Dissection of the poly(glu60 ala30 tyr10) (GAT)-specific T-cell repertoire in H-2Ik mice. I. GAT plus self-I-Ak-reactive T-cell clones can recognize alloactivating and/or restriction determinants on nonself-Ia molecules.
We examined the antigen recognition of the class II major histocompatibility complex (MHC) of 45 poly(glu60 ala30 tyr10) (GAT)-reactive T-cell clones isolated by limiting dilution cloning of a pool of in vivo-primed and in vitro-restimulated A.TL lymph-node T cells. Each clone expressed the Thy-1.2+, Lyt-1+, Lyt-2-, LFA-1+, Ia-, and H-2Dd+ cell-surface phenotype and exhibited strict specificity for GAT on syngeneic antigen-presenting cells (APCs). The monitoring of the proliferative responses of these clones in the presence or absence of GAT, using APCs from strains with 11 independent H-2 haplotypes, revealed several distinct specificity patterns: (i) most (31 of 45, 73%) T-cell clones recognized GAT in a self-I-Ak-restricted manner; (ii) other alloreactive clones (5 of 45, 11%) were stimulated to proliferate, irrespective of the presence of GAT, in response to allodeterminants expressed on H-2s, H-2d, H-2f or H-2u spleen cells; (iii) a third T-cell clone subset (4 of 45, 9%) was activated by GAT in the context of not only self-I-Ak but also nonself restriction Ia determinants; and (iv) three clones (7%) exhibited a triple specificity, i.e., they recognized GAT in the context of self and nonself Ia determinants and were alloreactive. One of the latter clones responded to GAT in an apparently non-MHC-restricted manner and recognized an I-Ab allodeterminant. These data provide direct evidence that the antigen-specific and alloreactive T-cell repertoires overlap and that the self-MHC restriction of GAT-specific T-cell responses is not absolute in A.TL mice.
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D002478:Cells, Cultured; D002999:Clone Cells; D000939:Epitopes / Q000032:analysis*; D005434:Flow Cytometry; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics*; D007519:Isoantigens / Q000235:genetics; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides; D010641:Phenotype; D011108:Polymers; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*
D000954:Antigens, Surface; D000939:Epitopes; D006183:H-2 Antigens; D007519:Isoantigens; D010455:Peptides; D011108:Polymers; C020749:GAT