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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. transplantation antigens antigen processing CD4 T cells GVHD Footnotes ↵ * Abbreviations used in this paper: BMDC, bone marrow–derived immature DC; DC, dendritic cell. H. Sahara's present address is Marine Biomedical Institute, Sapporo Medical University School of Medicine, Rishirifuji-cho, Hokkaido 097-0101, Japan. Submitted: 12 November 2002 Accepted: 20 December 2002
The Journal of Experimental Medicine – Rockefeller University Press
Published: Feb 3, 2003
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