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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Viret, C. Articles by Janeway, C. A. Search for Related Content PubMed PubMed Citation Articles by Viret, C. Articles by Janeway, C. A., Jr.

Functional and Phenotypic Evidence for Presentation of E_52–68 Structurally Related Self-Peptide(s) in I-E-Deficient Mice¹

Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510

The Y-Ae mAb and the 1H3.1 TCR-ß (V1/Vß6) are two immune receptors specific for I-A^b MHC class II molecules complexed to the 52–68 fragment of the -chain of I-E class II molecules (the E_52–68 peptide). A profound intrathymic negative selection occurs in 1H3.1 TCR transgenic mice in the presence of an I-E transgene. The administration of mAbs to 1H3.1/I-E double-transgenic newborn mice reveals that Y-Ae, but not the isotype-matched anti-I-E Y17 mAb, rescues a significant number of mature (Vß6^highCD4⁺CD8^-) thymocytes and allows the detection of E_52–68-reactive T cells in the periphery. These observations indicate that deletion of autoreactive T cells can be specifically inhibited in vivo by an mAb specific for the deleting self-peptide:self-MHC class II complex. Similar inhibition experiments indicate that C57BL/6 (I-A^b+/I-E^-) mice constitutively express an E-independent, Y-Ae-recognizable epitope(s). This finding is confirmed by the phenotypic analysis of mature (MHC class II high) C57BL/6 bone marrow-derived dendritic cells. Collectively, these observations further illustrate the peptide specificity of negative selection and demonstrate that MHC class II-positive cells from unmanipulated C57BL/6 mice that lack a functional I-E gene can assemble one or more self-peptide:I-A^b complexes recognizable by the E_52–68:I-A^b complex-specific Y-Ae mAb.