Human and Murine Clonal CD8+ T Cell Expansions Arise during Tuberculosis Because of TCR Selection

• DOI: 10.1371/journal.ppat.1004849
• Publication Date: 2015-05-06T17:57:55Z
• Authors: Cláudio Nunes-Alves; Matthew G. Booty; Stephen M. Carpenter; Alissa C. Rothchild; Constance J. Martin; Danielle Desjardins; Katherine Steblenko; Henrik N. Kløverpris; Rajhmun Madansein; Duran Ramsuran; Alasdair Leslie; Margarida Correia...; Samuel M. Behar
• Keywords: Immunodominance

The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. host factors that affect immunodominance incompletely understood. Whether epitopes elicit protective CD8+ or instead act as decoys subvert immunity and allow pathogens establish chronic infection is unknown. Here we show anatomically distinct human granulomas contain clonally expanded cells with overlapping receptor (TCR) repertoires. Similarly, the murine response M. tuberculosis dominated by TB10.44-11-specific extreme TCRβ bias. Using retrogenic model cells, TCR dominance arise because competition between clonotypes driven differences in affinity. Finally, demonstrate TB10.4-specific mediate protection which requires interferon-γ production TAP1-dependent antigen presentation vivo. Our study how immunodominance, biased repertoires, inter-related, provides new way measure quality immunity, if applied vaccine evaluation, could enhance our understanding immunity.