T cell activation is a tightly regulated event involving complex receptor-ligand interactions, ultimately leading to downstream signaling events. Optimal activation of naïve T cells requires at least two signals, antigen recognition and costimulation. The TCR complex, which recognizes antigenic peptides presented by MHC molecules, is critical in maintaining the specificity of the immune response. Signal two, or costimulation, is an antigen-independent signal required for sustained cell proliferation, effector/memory cell generation and prevention of anergy or apoptosis. The sole expression of costimulatory molecules on professional antigen presenting cells (APCs) ensures that only pathogen-specific T cells are activated and minimizes the chances of acquired immune responses being mounted against self.
|
|
|
Numerous costimulatory molecules have been identified playing a role in the initiation of immune responses by T and B lymphocytes. Signals provided through CD28-B7 interactions are essential for initial naïve T cell activation leading to increased IL-2 production and IL-2Rα (CD25) expression. NKG2D binds to the MHC-related proteins MIC and Rae-1 and induces IL-2 production and proliferation. In other cell types, such as B cells, activation requires CD40-CD40L interactions for proper antibody response: promoting survival, cytokine receptor expression, and inducing antibody class switch. In addition to the costimulatory pathways that are important in naïve lymphocyte activation, other costimulatory molecules play a role in effector/memory lymphocyte activation.
The costimulatory receptors ICOS, OX-40, 4-1BB, and CD27 bind to their ligands B7h, OX-40L, 4-1BBL, and CD70, respectively, to enhance the activation, survival, and cytokine
secretion of effector/memory, but not naïve T and B cells. These costimulatory receptors and their ligands are not constitutively expressed but are induced on differentiated T cells, and their ligands are not restricted to APCs. T cell activation generally incorporates a self-limiting mechanism, such as inhibitory costimulators, to regulate T cell tolerance and attenuate the immune response. The expanding set of inhibitory costimulators currently includes CTLA-4 (CD152), PD-1, and BTLA. While expression of these molecules is induced following T cell activation, they are absent on naïve T cells. Lastly, B7-H3 is a new costimulatory ligand originally described to induce T cell proliferation and IFN-γ production through an as of yet unidentified receptor. The recent generation of B7-H3-deficient mice, however, suggests that it is an inhibitory costimulator.
As positive costimulation can enhance T and B cell activation, inhibitory costimulation can just as strongly attenuate these responses. The final outcome of an immune response likely depends on the balance between these positive and negative signals.
Human, Mouse & Rat Costimulatory Molecules
Table 1: Human Costimulatory Molecules
|
Human Costimulatory Molecules
|
| Human |
Clone |
SKU |
Formats |
| CD2
|
RPA-2.10
|
0029
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5
|
| CD3
|
OKT3
|
0037
|
Purified, FG Purified, FITC, PE, Alexa Fluor® 647, Alexa Fluor® 488, Pacific Blue®
|
|
|
UCHT1
|
0038
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, APC-Cy7, PE-Cy7
|
|
|
HIT3a
|
0039
|
Purified, FG Purified, FITC, PE
|
| CD4
|
OKT4
|
0048
|
Purified, FG Purified, Biotin, FITC, PE, APC, Alexa Fluor® 647, Alexa Fluor® 488, Pacific Blue®
|
|
|
RPA-T4
|
0049
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, APC-Cy7, PE-Cy7
|
| CD8a
|
OKT8
|
0086
|
Purified, FG Purified, Biotin, FITC, PE, APC, Alexa Fluor® 647, Alexa Fluor® 488, Pacific Blue®
|
|
|
HIT8a
|
0089
|
Purified, FG Purified, Biotin, FITC, PE
|
|
|
RPA-T8
|
0088
|
Purified, FITC, PE, PE-Cy5, APC, APC-Cy7, PE-Cy7
|
| CD11a
|
HI111
|
0119
|
Purified, FG Purified, FITC, PE
|
| CD11b
|
CBRM1/5
|
0113
|
Purified, FG Purified, FITC, PE, Alexa Fluor® 700
|
|
|
ICRF44
|
0118
|
Purified, Biotin, PE, PE-Cy7
|
| CD11c
|
3.9
|
0116
|
Purified, Biotin, FITC, PE, APC, PE-Cy7
|
| CD19
|
HIB19
|
0199
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, APC-Cy7, PE-Cy7, Alexa Fluor® 647, Alexa Fluor® 488, Alexa Fluor® 700, Pacific Blue®
|
| CD20
|
2H7
|
0209
|
Purified, FITC, PE, PE-Cy5, PE-Cy7, APC, APC-Cy7, Alexa Fluor® 700, Pacific Blue®
|
| CD25 (IL-2R\alpha)
|
BC96
|
0259
|
Purified, Biotin, FITC, PE, PE-Cy5, APC, PE-Cy7
|
| CD26
|
2A6
|
0269
|
Purified, FITC, PE
|
| CD27
|
O323
|
0279
|
Purified, Biotin, FITC, PE, APC, APC-Cy7, Alexa Fluor® 700
|
|
|
LG.7F9
|
0271
|
Purified, FG Purified, Biotin, FITC, PE, APC
|
| CD28
|
CD28.2 (costimulatory)
|
0289
|
Purified, FG Purified, Biotin, FITC, PE, APC, PE-Cy7
|
|
|
CD28.6 (blocking)
|
0288
|
FG Purified
|
| CD40
|
5C3
|
0409
|
Purified, FG Purified, FITC, PE
|
| CD44
|
IM7
|
0441
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, PE-Cy7, APC-Cy7, PE-Cy5.5, Alexa Fluor® 700,
Pacific Blue®
|
| CD54
|
HA58
|
0549
|
Purified, FG Purified, Biotin, PE
|
| CD62L (L-Selectin)
|
DREG56
|
0629
|
Purified, FG Purified, FITC, PE, PE-Cy5, APC, APC-Cy7, PE-Cy7
|
| CD69 (VEA)
|
FN50
|
0699
|
Purified, Biotin, FITC, PE, APC, PE-Cy7
|
| CD80 (B7.1)
|
2D10.4
|
0809
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5
|
| CD83
|
HB15e
|
0839
|
Purified, Biotin, FITC, PE
|
| CD86 (B7.2)
|
IT2.2
|
0869
|
Purified, FG Purified, Biotin, PE, PE-Cy5
|
| CD95 (Fas)
|
EOS9.1
|
0958
|
Purified, FG Purified
|
|
|
DX2
|
0959
|
Purified, Biotin, FITC, PE, PE-Cy5
|
| CD134 (OX-40)
|
ACT35
|
1347
|
Purified, FITC, PE, APC
|
| CD150 (SLAM)
|
A12 (7D4)
|
1509
|
Purified, FG Purified, Biotin, FITC, PE
|
| CD152 (CTLA-4)
|
14D3
|
1529
|
Purified, FG Purified, Biotin, PE
|
| CD154 (CD40L)
|
24-31
|
1548
|
Purified, FG Purified, FITC, PE
|
| CD178 (FasL)
|
NOK-1
|
9919
|
Purified, FG Purified, Biotin, PE
|
| CD209 (DC-SIGN)
|
eB-h209
|
2099
|
Purified, Biotin, FITC, PE, APC
|
| CD277
|
eBioBT3.1
|
2779
|
Purified, Biotin, PE
|
| AITR
|
eBioAITR
|
5875
|
Purified, APC
|
| AITRL
|
eBioAITR-L
|
5475
|
Purified, Biotin
|
| B7-H3
|
M3.2D7
|
5973
|
Purified, FG Purified, Biotin, PE
|
| B7-H4
|
H74
|
5949
|
Purified, FG Purified, Biotin, PE
|
| BTLA
|
MIH26
|
5979
|
Purified, FG Purified, Biotin, PE
|
| HLA-ABC
|
W6/32
|
9983
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5
|
| HLA-DR
|
LN3
|
9956
|
Purified, PE, APC, PE-Cy7, Alexa Fluor® 700
|
| ICOS
|
ISA-3
|
9948
|
Purified, FG Purified, Biotin, FITC, PE
|
| ICOSL (B7RP-1)
|
MIH12
|
5889
|
Purified, FG Purified, Biotin, PE
|
| NKG2D
|
1D11 (activating)
|
5878
|
Purified, FG Purified, Biotin, FITC, PE, APC
|
|
|
5C6 (activating)
|
5879
|
Purified, FG Purified, Biotin, PE
|
| PD-1 (CD279)
|
J116
|
9989
|
Purified, FG Purified
|
|
|
MIH4
|
9969
|
Purified, PE, Alexa Fluor® 647
|
| PD-L1 (B7-H1)
|
MIH1
|
5983
|
Purified, FG Purified, Biotin, PE, APC, PE-Cy7
|
| PD-L2 (B7-DC)
|
MIH18
|
5888
|
Purified, FG Purified, Biotin, PE
|
| TCR\alpha\beta
|
IP26
|
9986
|
Purified, Biotin, FITC, PE, PE-Cy5, APC
|
| TCR\gamma\delta
|
B1.1
|
9959
|
Purified, FG Purified, Biotin, FITC, PE
|
| ZAP-70
|
1E7.2
|
6695
|
Purified, Biotin, FITC, PE, PE-Cy5.5
|
| *Alexa Fluor® and Pacific Blue® are registered trademarks of and licensed under patents assigned to Molecular Probes, Inc. for research use only. |
Table 2: Mouse Costimulatory Molecules
|
Mouse Costimulatory Molecules
|
| Mouse |
Clone |
SKU |
Formats |
| CD2
|
RM2-5
|
0021
|
Purified, FG Purified, Biotin, FITC, PE
|
| CD3\epsilon
|
145-2C11
|
0031
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, PE-Cy7, PE-Cy5.5, FG Biotin, Alexa Fluor® 488
|
|
|
17A2
|
0032
|
Purified, FG Purified, APC-Cy7, Alexa Fluor® 647, Alexa Fluor® 700, Pacific Blue®
|
| CD4
|
GK1.5
|
0041
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, Cy5, PE-Cy7, FG Biotin, Alexa Fluor® 647,
Alexa Fluor® 488, Alexa Fluor® 700
|
|
|
RM4-5
|
0042
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, APC-Cy7, PE-Cy7, APC-Cy5.5, PE-Cy5.5,
Alexa Fluor® 700, Pacific Blue®
|
|
|
RM4-4
|
0043
|
Purified, Biotin, FITC, PE
|
| CD5
|
53-7.3
|
0051
|
Purified, Biotin, FITC, PE, APC
|
| CD8a
|
53-6.7
|
0081
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, PE-Cy7, APC-Cy7, Cy5, FG Biotin, Alexa Fluor® 647,
Alexa Fluor® 488, Alexa Fluor® 700, Pacific Blue®
|
| CD8b
|
CT-CD8b
|
0082
|
Purified, Biotin, FITC, PE, PE-Cy5, APC
|
|
|
eBioH35-17.2
|
0083
|
Purified, Biotin, FITC, PE, PE-Cy5, APC
|
| CD11a
|
M17/4
|
0111
|
Purified, FG Purified, Biotin, FITC, PE
|
| CD11b
|
M1/70
|
0112
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, Cy5, APC-Cy7, PE-Cy7, FG Biotin, Alexa Fluor® 647,
Alexa Fluor® 488, Pacific Blue®
|
| CD11c
|
N418
|
0114
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, PE-Cy7, PE-Cy5.5, Alexa Fluor® 647, Alexa Fluor® 488, Alexa Fluor® 700, Pacific Blue®
|
| CD19
|
6D5
|
0192
|
Purified, FG Purified, PE, PE-Cy5, APC-Cy5.5, PE-Cy5.5
|
|
|
MB19-1
|
0191
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, FG Biotin
|
| CD24 (HSA)
|
M1/69
|
0242
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5
|
|
|
30-F1
|
0241
|
Purified, FITC, PE
|
| CD25 (IL-2R\alpha)
|
PC61.5
|
0251
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, APC-Cy7, PE-Cy7, FG Biotin
|
| CD27
|
LG.7F9
|
0271
|
Purified, FG Purified, Biotin, FITC, PE, APC
|
| CD28
|
37.51
|
0281
|
Purified, FG Purified, Biotin, PE, PE-Cy5, APC, PE-Cy7
|
| CD30
|
mCD30.1
|
0301
|
Purified, FG Purified, Biotin, PE
|
| CD40
|
HM40-3
|
0402
|
Purified, FG Purified, Biotin, FITC
|
|
|
1C10
|
0401
|
Purified, FG Purified, Biotin, PE, PE-Cy5, APC
|
| CD44
|
IM7
|
0441
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, APC-Cy7, PE-Cy7, PE-Cy5.5, Alexa Fluor® 700,
Pacific Blue®
|
| CD54 (ICAM-1)
|
YN1/1.7.4
|
0541
|
Purified, FG Purified, Biotin, FITC, PE
|
|
|
eBioKAT-1
|
0542
|
Purified, FG Purified, PE
|
| CD62L (L-Selectin)
|
MEL-14
|
0621
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, APC-Cy7, PE-Cy7, PE-Cy5.5, Alexa Fluor® 700,
Pacific Blue®
|
| CD69 (VEA)
|
H1.2F3
|
0691
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, PE-Cy7
|
| CD70 (CD27L)
|
FR70
|
0701
|
Purified, FG Purified, Biotin, PE
|
| CD80 (B7.1)
|
16-10A1
|
0801
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC
|
| CD81 (TAPA-1)
|
Eat-2
|
0811
|
Purified, FG Purified, Biotin
|
| CD83
|
Michel17
|
0831
|
Purified, Biotin, FITC, PE
|
| CD86 (B7.2)
|
PO3.1
|
0861
|
Purified, FG Purified, PE
|
|
|
GL1
|
0862
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC
|
| CD90 (Thy1)
|
G7
|
0901
|
Purified, FG Purified
|
| CD90.1
|
HIS51
|
0900
|
Purified, Biotin, FITC, PE, PE-Cy5, APC, PE-Cy7
|
| CD90.2
|
53-2.1
|
0902
|
Purified, Biotin, FITC, PE, PE-Cy5, APC, PE-Cy7
|
|
|
30-H12
|
0903
|
Purified, FG Purified, Biotin, FITC, PE
|
| CD95 (Fas)
|
15A7
|
0951
|
Purified, Biotin, PE
|
| CD122 (IL-2R\beta)
|
5H4
|
1221
|
Purified, FG Purified, Biotin, PE
|
|
|
TM-b1
|
1222
|
Purified, FG Purified, Biotin, FITC, PE
|
| CD134 (OX-40)
|
OX-86
|
1341
|
Purified, FG Purified, Biotin, PE
|
| CD137 (4-1BB)
|
17B5
|
1371
|
Purified, FG Purified, Biotin, PE
|
| CD150 (SLAM)
|
9D1
|
1501
|
Purified, FG Purified, Biotin, FITC, PE, APC
|
| CD152 (CTLA-4)
|
UC10-4B9
|
1522
|
Purified, FG Purified, Biotin, PE
|
|
|
9H10
|
1521
|
Purified, FG Purified
|
| CD153 (CD30L)
|
RM153
|
1531
|
Purified, FG Purified, Biotin, PE
|
| CD154 (CD40L)
|
MR1
|
1541
|
Purified, FG Purified, Biotin, PE
|
| CD178 (FasL)
|
MFL3
|
5911
|
Purified, FG Purified, Biotin, PE
|
|
|
MFL4
|
5912
|
Purified, FG Purified
|
| CD209 (DC-SIGN)
|
5H10
|
2091
|
Purified, Biotin, PE
|
|
|
LWC06
|
2092
|
Purified, Biotin, FITC, PE
|
| 4-1BBL
|
TKS-1
|
5901
|
Purified, FG Purified, Biotin, PE
|
| B7-H3
|
M3.2D7
|
5973
|
Purified, FG Purified, Biotin, PE
|
| B7-H4
|
188
|
5972
|
Purified, FG Purified, Biotin, PE
|
|
|
clone 9
|
5970
|
Purified, Biotin, PE
|
|
|
eBioMIH29
|
5470
|
Purified, PE
|
| BTLA
|
6F7 (blocking)
|
5950
|
Purified, FG Purified, Biotin, PE
|
|
|
3F9.D12
|
5953
|
Purified
|
|
|
6H6
|
5954
|
Purified
|
|
|
6G3
|
5955
|
Purified
|
|
|
8F4 (non-blocking)
|
5956
|
Purified, Biotin, PE
|
| GITR
|
DTA-1
|
5874
|
Purified, FG Purified, Biotin, FITC, PE, APC
|
| GITRL
|
eBioYGL386
|
5854
|
Purified, Biotin, PE
|
| ICOS
|
C398.4A
|
9949
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5
|
|
|
7E.17G9
|
9942
|
Purified, FG Purified, Biotin, PE, PE-Cy5
|
|
|
15F9
|
9940
|
Purified, Biotin, PE, PE-Cy5
|
| ICOSL (B7RP-1)
|
HK5.3
|
5985
|
Purified, FG Purified, Biotin, PE
|
| MHC class I
|
28-14-8
|
5999
|
Purified, FG Purified, Biotin, FITC, PE
|
|
|
34-1-2S
|
5998
|
Purified, FG Purified, Biotin, FITC, PE
|
| MHC class II
|
M5/114.15.2
|
5321
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, FG Biotin, Alexa Fluor® 700
|
|
|
14-4-4S
|
5980
|
Purified, Biotin, FITC, PE
|
| NKG2D
|
A10 (activating)
|
5872
|
Purified, FG Purified, PE
|
|
|
C7 (blocking)
|
5873
|
Purified, FG Purified, Biotin, PE
|
|
|
CX5 (blocking)
|
5882
|
Purified, FG Purified, Biotin, PE, APC, PE-Cy7
|
|
|
MI6 (blocking)
|
5880
|
Purified, FG Purified, Biotin
|
| OX-40L
|
RM134L
|
5905
|
Purified, FG Purified, Biotin, PE
|
| PD-1
|
RMP1-14
|
9982
|
Purified, FG Purified
|
|
|
RMP1-30
|
9981
|
Purified, FG Purified, Biotin, FITC, PE
|
|
|
J43
|
9985
|
Purified, FG Purified, Biotin, FITC, PE
|
| PD-L1 (B7-H1)
|
1-111A
|
9971
|
Purified, Biotin
|
|
|
MIH5
|
5982
|
Purified, FG Purified, Biotin, PE
|
| PD-L2 (B7-DC)
|
122
|
9972
|
Purified, Biotin, FITC, PE
|
|
|
TY25
|
5986
|
Purified, FG Purified, Biotin, PE
|
| RAE-1\gamma
|
CX1
|
5881
|
Purified, FG Purified, Biotin, PE
|
| TCR\beta
|
H57-597
|
5961
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5, APC, APC-Cy7, PE-Cy5.5, FG Biotin
|
| TCR\gamma\delta
|
UC7-13D5
|
5811
|
Purified, FG Purified, Biotin, FITC, FG Biotin
|
| ZAP-70
|
1E7.2
|
6695
|
Purified, Biotin, FITC, PE, PE-Cy5.5
|
| *Alexa Fluor® and Pacific Blue® are registered trademarks of and licensed under patents assigned to Molecular Probes, Inc. for research use only. |
Table 3: Rat Costimulatory Molecules
|
Rat Costimulatory Molecules
|
| Rat |
Clone |
SKU |
Formats |
| CD3
|
eBioG4.18
|
0030
|
Purified, FG Purified, Biotin, FITC, PE
|
| CD5
|
HIS47
|
0050
|
Purified, FITC, PE, PE-Cy5, APC
|
| CD27
|
LG.7F9
|
0271
|
Purified, FG Purified, Biotin, FITC, PE, APC
|
| CD28
|
JJ319
|
0280
|
Purified, FG Purified, FITC, PE
|
| CD80 (B7.1)
|
3H5
|
0800
|
Purified, FG Purified, Biotin, PE
|
| CD81 (TAPA-1)
|
Eat-2
|
0811
|
Purified, FG Purified, Biotin
|
| CD86 (B7.2)
|
24F
|
0860
|
Purified, FG Purified, Biotin, FITC, PE
|
| CD90.1 (Thy1.1)
|
HIS51
|
0900
|
Purified, Biotin, FITC, PE, PE-Cy5, APC, PE-Cy7
|
| CD152 (CTLA-4)
|
WKH203
|
1520
|
Purified, Biotin, PE
|
| CD178 (FasL)
|
MFL4
|
5912
|
Purified, FG Purified
|
| OX-40L
|
ATM2
|
1340
|
Purified, FG Purified, Biotin, PE
|
| ICOS
|
C398.4A
|
9949
|
Purified, FG Purified, Biotin, FITC, PE, PE-Cy5
|
| MHC class II
|
14-4-4S
|
5980
|
Purified, Biotin, FITC, PE
|
|
|
HIS19
|
0920
|
Purified, Biotin, FITC, PE, APC
|
| OX-40L
|
ATM2
|
1340
|
Purified, FG Purified, Biotin, PE
|
| TCR\alpha\beta
|
R73
|
5960
|
Purified, FG Purified, Biotin, FITC, PE
|
| TCR\gamma\delta
|
V65
|
5810
|
Purified, Biotin, FITC, PE
|
| *Alexa Fluor® and Pacific Blue® are registered trademarks of and licensed under patents assigned to Molecular Probes, Inc. for research use only. |
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Liang, L., et al. The right place at the right time: novel B7 famly members regulate effector T cell responses. Curr Opin Immunol. 2002 Jun;14(3):384-90. [PubMed]
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Carreno, B.M., et al. The B7 family of ligands and its receptors: new pathways for costimulation and inhibition of immune responses. Annu Rev Immunol. 2002;20:29-53. [PubMed]
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Croft, M. Co-stimulatory members of the TNFR family: keys to effective T-cell immunity? Nat Rev Immunol. 2003 Aug;3(8):609-20. [PubMed]
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Lohr, J., et al. The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens. Nat Immunol. 2003 Jul;4(7):664-9. [PubMed]
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