Replacement of TCR Dβ With Immunoglobulin D H DSP2.3 Imposes a Tyrosine-Enriched TCR Repertoire and Adversely Affects T Cell Development.

Autor: Levinson M; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States., Khass M; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.; Division of Genetic Engineering and Biotechnology, National Research Center, Cairo, Egypt., Burrows PD; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States., Schroeder HW Jr; Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2020 Sep 29; Vol. 11, pp. 573413. Date of Electronic Publication: 2020 Sep 29 (Print Publication: 2020).
DOI: 10.3389/fimmu.2020.573413
Abstrakt: Enrichment for tyrosine in immunoglobulin CDR-H3 is due in large part to natural selection of germline immunoglobulin D H sequence. We have previously shown that when D H sequence is modified to reduce the contribution of tyrosine codons, epitope recognition is altered and B cell development, antibody production, autoantibody production, and morbidity and mortality following pathogen challenge are adversely affected. TCRβ diversity (Dβ) gene segment sequences are even more highly conserved than D H , with trout Dβ1 identical to human and mouse Dβ1. We hypothesized that natural selection of Dβ sequence also shapes CDR-B3 diversity and influences T cell development and T cell function. To test this, we used a mouse strain that lacked Dβ2 and contained a novel Dβ1 allele ( DβYTL ) that replaces Dβ1 with an immunoglobulin D H , DSP2.3. Unlike Dβ1, wherein glycine predominates in all three reading frames (RFs), in DSP2.3 there is enrichment for tyrosine in RF1, threonine in RF2, and leucine in RF3. Mature T cells using DβYTL expressed TCRs enriched at particular CDR-B3 positions for tyrosine but depleted of leucine. Changing Dβ sequence altered thymocyte and peripheral T cell numbers and the T cell response to an ovalbumin immunodominant epitope. The differences in tyrosine content might explain, at least in part, why TCRs are more polyspecific and of lower affinity for their cognate antigens than their immunoglobulin counterparts.
(Copyright © 2020 Levinson, Khass, Burrows and Schroeder.)
Databáze: MEDLINE
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