I-A alpha polymorphic residues that determine alloreactive T cell recognition.
An individual's T lymphocytes are highly reactive to allogeneic MHC molecules. As a step in deciphering the mechanism of allorecognition by T lymphocytes, we have attempted to identify the TCR's target on MHC class II molecules, in particular the polymorphic residues that determine the specificity of recognition. We have generated a panel of Ak-reactive, Ab-nonreactive T cell hybridomas, and sets of L cell transfectants displaying A alpha A beta molecules with wild-type, chimeric or single site-mutated A alpha chains, with reciprocal interchanges between Ak and Ab. We then measured the stimulation of the T hybridomas in response to the transfectants. The results indicate that the hybridomas recognize diverse and complex determinants, with contributions from both A alpha and A beta chains, and from several regions or amino acids of the A alpha chain. The data are most consistent with a model in which alloreactivity results from the presentation of peptides to the T cell by an allogeneic MHC molecule, peptides that cannot be presented by the responder's own MHC complexes. The specificity of allorecognition seems to be imparted mainly by peptide/MHC molecule rather than TCR/MHC molecule contacts.
Pierres
M
M
Centre d'Immunologie Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique de Marseille-Luminy, France.
Marchetto
S
S
Naquet
P
P
Landais
D
D
Peccoud
J
J
Benoist
C
C
Mathis
D
D
D000818:Animals; D004247:DNA / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D007126:Immunoglobulin Allotypes / Q000276:immunology*; D007739:L Cells; D046911:Macromolecular Substances; D051379:Mice; D009154:Mutation; D011110:Polymorphism, Genetic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007126:Immunoglobulin Allotypes; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell; D004247:DNA