Second class minors: molecular identification of the autosomal H46 histocompatibility locus as a peptide presented by major histocompatibility complex class II molecules.
CD4 T cells regulate immune responses that cause chronic graft rejection and graft versus host disease but their target antigens remain virtually unknown. We developed a new method to identify CD4 T cell-stimulating antigens. LacZ-inducible CD4 T cells were used as a probe to detect their cognate peptide/MHC II ligand generated in dendritic cells fed with Escherichia coli expressing a library of target cell genes. The murine H46 locus on chromosome 7 was thus found to encode the interleukin 4-induced IL4i1 gene. The IL4i1 precursor contains the HAFVEAIPELQGHV peptide which is presented by A(b) major histocompatibility complex class II molecule via an endogenous pathway in professional antigen presenting cells. Both allelic peptides bind A(b) and a single alanine to methionine substitution at p2 defines nonself. These results reveal novel features of H loci that regulate CD4 T cell responses as well as provide a general strategy for identifying elusive antigens that elicit CD4 T cell responses to tumors or self-tissues in autoimmunity.
Sahara
Hiroeki
H
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Shastri
Nilabh
N
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D005420:Flavoproteins / Q000235:genetics* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006825:Hybridomas / Q000276:immunology; D066298:In Vitro Techniques; D050830:L-Amino Acid Oxidase; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008912:Minor Histocompatibility Loci; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D014181:Transplantation Immunology
D018076:DNA, Complementary; D005420:Flavoproteins; D000949:Histocompatibility Antigens Class II; C484538:Il4i1 protein, mouse; D050830:L-Amino Acid Oxidase