Involvement of major histocompatibility complex products in tolerance induction in the thymus.
KJ23a+ T cell clones, which bear the determinant encoded by the V beta 17a T cell receptor gene segment, frequently recognize IE molecules of various murine H-2 haplotypes. In the presence of IE molecules, thymic maturation of KJ23a+ clones is infrequent. We investigated the basis of this phenomenon by blocking expression of IE molecules with monoclonal anti-IE antibodies in organ cultures of fetal thymus and in neonates from the C57BR/cdJ strain (H-2k, V beta 17a homozygous). Our data support the contention that this process results from deletion of clones with anti-IE reactivity, as functional blocking of the IE molecule results in maturation of IE-reactive clones and increased numbers of KJ23a+ mature cells. In addition, we noted that blocking of functional IE expression in this haplotype permitted development of both CD4+/KJ23a+ and CD8+/KJ23a+ T cells. The CD4+ clones isolated from anti-IE-treated animals were frequently reactive against IEk; we could demonstrate no alloreactivity against B cell or B lymphoma stimulators in the CD4- clones. We conclude that clonal deletion events during thymic development may be initiated by T cell precursor interactions with MHC molecules against which the mature clones display no measurable reactivity. Specifically, clones destined to be MHC Class I-reactive may be deleted during development by interactions with MHC Class II molecules.
McDuffie
M
M
Howard Hughes Medical Institute, Department of Medicine, Denver, CO.
Roehm
N
N
Kappler
J W
JW
Marrack
P
P
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000502:physiology; D002454:Cell Differentiation; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007958:Leukocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000502:physiology
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D011948:Receptors, Antigen, T-Cell