Abstract:
:We performed a quantitative analysis of the HLA restriction, antigen and epitope specificity of human pathogen specific responses in healthy individuals infected with M. tuberculosis (Mtb), in a South African cohort as a test case. The results estimate the breadth of T cell responses for the first time in the context of an infection and human population setting. We determined the epitope repertoire of eleven representative Mtb antigens and a large panel of previously defined Mtb epitopes. We estimated that our analytic methods detected 50-75% of the total response in a cohort of 63 individuals. As expected, responses were highly heterogeneous, with responses to a total of 125 epitopes detected. The 66 top epitopes provided 80% coverage of the responses identified in our study. Using a panel of 48 HLA class II-transfected antigen-presenting cells, we determined HLA class II restrictions for 278 epitope/donor recognition events (36% of the total). The majority of epitopes were restricted by multiple HLA alleles, and 380 different epitope/HLA combinations comprised less than 30% of the estimated Mtb-specific response. Our results underline the complexity of human T cell responses at a population level. Efforts to capture and characterize this broad and highly HLA promiscuous Mtb-specific T cell epitope repertoire will require significant peptide multiplexing efforts. We show that a comprehensive "megapool" of Mtb peptides captured a large fraction of the Mtb-specific T cells and can be used to characterize this response.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Lindestam Arlehamn CS,McKinney DM,Carpenter C,Paul S,Rozot V,Makgotlho E,Gregg Y,van Rooyen M,Ernst JD,Hatherill M,Hanekom WA,Peters B,Scriba TJ,Sette Adoi
10.1371/journal.ppat.1005760subject
Has Abstractpub_date
2016-07-13 00:00:00pages
e1005760issue
7eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-16-00800journal_volume
12pub_type
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