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Negative selection and peptide chemistry determine the size of naive foreign peptide-MHC class II-specific CD4+ T cell populations.
Title | Negative selection and peptide chemistry determine the size of naive foreign peptide-MHC class II-specific CD4+ T cell populations. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | H Chu, H, Moon, JJ, Kruse, AC, Pepper, M, Jenkins, MK |
Journal | J Immunol |
Volume | 185 |
Issue | 8 |
Pagination | 4705-13 |
Date Published | 2010 Oct 15 |
ISSN | 1550-6606 |
Keywords | Animals, Antigens, CD4-Positive T-Lymphocytes, Cell Count, Histocompatibility Antigens Class II, Lymphocyte Activation, Mice, Mice, Knockout, Peptides, Receptors, Antigen, T-Cell |
Abstract | Naive CD4(+) T cell populations that express TCRs specific for different foreign peptide-MHC class II complex (pMHCII) ligands can vary in size over several orders of magnitude. This variation may explain why immune responses to some peptides are stronger than others. In this study, we used a sensitive pMHCII-tetramer-based cell enrichment method to study the derivation of two naive foreign pMHCII-specific naive CD4(+) T cell populations that differed in size by 8-fold in normal mice. Analysis of mice in which thymic negative selection was impaired revealed that the smaller population underwent more clonal deletion than the larger population. In addition, large naive cell populations tended to recognize peptides with tryptophan residues as TCR contacts. Thus, the foreign pMHCII that tend to be recognized by large naive populations induce minimal clonal deletion and contain certain amino acids with the capacity to interact favorably with TCRs. |
DOI | 10.4049/jimmunol.1002276 |
Alternate Journal | J. Immunol. |
PubMed ID | 20861357 |
PubMed Central ID | PMC3510669 |
Grant List | P01 AI35296 / AI / NIAID NIH HHS / United States R01 AI039614 / AI / NIAID NIH HHS / United States R01 AI39614 / AI / NIAID NIH HHS / United States R37 AI027998 / AI / NIAID NIH HHS / United States R37 AI27998 / AI / NIAID NIH HHS / United States |