Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors.
B7-0 or B7-2 (CD86) is a T cell costimulatory molecule that binds the same receptors (CD28 and CTLA-4) as B7-1 (CD80), but shares with it only approximately 25% sequence identity and is expressed earlier during an immune response. Here we show that human CD86 maintains similar (within approximately 2- to 3-fold) overall receptor binding and T cell costimulatory properties as CD80. However, CD80 and CD86 did not bind equivalently to CTLA-4: CD80 bound Y100A, a form of CTLA4lg with a mutation in the CDR3-like region, > 200-fold better than did CD86; inhibition of CD80-mediated cellular responses required approximately 100-fold lower CTLA4lg concentrations; and CD80-CTLA4lg complexes dissociated 5- to 8-fold more slowly, Thus, CD80 and CD86 utilize different binding determinants and have different kinetics of binding to CD28 and CTLA-4.
Linsley
P S
PS
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Greene
J L
JL
Brady
W
W
Bajorath
J
J
Ledbetter
J A
JA
Peach
R
R
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000737:chemistry / Q000378:metabolism*; D051940:B7-2 Antigen; D001483:Base Sequence; D001665:Binding Sites; D018106:CD28 Antigens / Q000737:chemistry / Q000378:metabolism*; D016466:CHO Cells; D060908:CTLA-4 Antigen; D006224:Cricetinae; D018076:DNA, Complementary; D006801:Humans; D018796:Immunoconjugates; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018076:DNA, Complementary; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D000069594:Abatacept