High prevalence of low affinity peptide–MHC II tetramer–negative effectors during polyclonal CD4+ T cell responses

• Type of Material: Article
• Authors: Joseph J. Sabatino, Jr., Emory University; Jun Huang, Georgia Institute of Technology; Cheng Zhu, Georgia Institute of Technology; Brian Evavold, Emory University
• Language: English
• Date: 2011-01-10
• Publisher: Rockefeller University Press
• Publication Version: Final Published Version
• Copyright Statement: © 2011 Sabatino et al.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://jem.rupress.org/content/208/1/81
• Title of Journal or Parent Work: Journal of Experimental Medicine
• ISSN: 0022-1007
• Volume: 208
• Issue: 1
• Start Page: 81
• End Page: 90
• Grant/Funding Information: This work was supported by National Multiple Sclerosis Society grant RG4047-A-3 and National Institutes of Health grants NS071518 (to B.D. Evavold) and AI38282 and AI060799 (to C. Zhu).
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

Abstract

T cell affinity for antigen initiates adaptive immunity. However, the contribution of low affinity cells to a response is unknown as it has not been possible to assess the entire affinity range of a polyclonal T cell repertoire. In this study, we used a highly sensitive two-dimensional binding assay to identify low affinity cells in polyclonal autoreactive and pathogen-reactive CD4+ T cell populations specific for myelin oligodendrocyte glycoprotein (MOG) and lymphocytic choriomeningitis virus (LCMV) antigens, respectively. Low affinity CD4+ T cells, below detection with peptide–major histocompatibility complex class II tetramers, were at least as frequent as high affinity responders and contributed significant effector cytokines in both primary antigen–specific responses. We further demonstrated that MOG- and LCMV-specific CD4+ T cells possessed similarly broad ranges in their affinities (>100-fold wide), only differing in the frequencies of low and high affinity cells. Thus, low as well as high affinity CD4+ T cells are critical effectors in autoimmune and pathogen-specific responses.