HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Suh, C.-H. Articles by Cohen, P. L. Search for Related Content PubMed PubMed Citation Articles by Suh, C.-H. Articles by Cohen, P. L. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Lupus

T Cell Reactivity to MHC Class II-Bound Self Peptides in Systemic Lupus Erythematosus-Prone MRL/lpr Mice ¹

Chang-Hee Suh^*, John H. Freed and Philip L. Cohen^2,*

^* Division of Rheumatology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and Division of Basic Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206

The epitopes recognized by pathogenic T cells in systemic autoimmune disease remain poorly defined. Certain MHC class II-bound self peptides from autoimmune MRL/lpr mice are not found in eluates from class II molecules of MHC-identical C3H mice. Eleven of 16 such peptides elicited lymph node cell and spleen cell T cell proliferation in both MRL/lpr (stimulation index = 2.03–5.01) and C3H mice (stimulation index = 2.03–3.75). IL-2 and IFN- production were detected, but not IL-4. In contrast to what was seen after immunization, four self peptides induced spleen cell proliferation of T cells from naive MRL/lpr, but not from C3H and C57BL/6.H2^k, mice. These peptides were derived from RNA splicing factor SRp20, histone H2A, ₂-microglobulin, and MHC class II I-A^k. The first three peptides were isolated from I-E^k molecules and the last peptide was bound to I-A^k. T cell responses, evident as early as 1 mo of age, depended on MHC class II binding motifs and were inhibited by anti-MHC class II Abs. Thus, although immunization can evoke peripheral self-reactive T cells in normal mice, the presence in MRL/lpr mice of spontaneous T cells reactive to certain MHC-bound self peptides suggests that these T cells actively participate in systemic autoimmunity. Peptides eluted from self MHC class II molecules may yield important clues to T cell epitopes in systemic autoimmunity.