Alloreactivity studied with mutants of HLA-A2.
Based on the crystal structure of HLA-A2.1 and the recognition of a panel of mutant HLA-A2.1 molecules by a large number of alloreactive cytotoxic T lymphocyte clones, a model to explain alloreactivity is described. In this model recognition of an allogeneic major histocompatibility complex molecule by a self-restricted T-cell receptor occurs as the result of accommodation by the receptor of a few amino acid differences in the major histocompatibility complex molecule--i.e., cross-recognition. Alloreactivity is the result of the presence in the foreign antigen binding site of the allogeneic major histocompatibility complex molecule of unusual self-peptides, reactivity to which could not have been eliminated by negative thymic selection.
Santos-Aguado
J
J
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
Crimmins
M A
MA
Mentzer
S J
SJ
Burakoff
S J
SJ
Strominger
J L
JL
D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000235:genetics; D008285:Major Histocompatibility Complex; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D015789:HLA-A2 Antigen; D007519:Isoantigens