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Role of individual's T ‐cell immunome in controlling HIV ‐1 progression
Author(s) -
Grifoni Alba,
Montesano Carla,
Palma Paolo,
Giovannetti Marta,
CastelliGattinara Guido,
Ciccozzi Massimo,
Mattei Maurizio,
Mancino Giorgio,
Salerno Alfredo,
Colizzi Vittorio,
Amicosante Massimo
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12344
Subject(s) - epitope , virology , human leukocyte antigen , biology , population , immunology , antigen , medicine , environmental health
Summary Viral and host factors can influence HIV ‐1 progression, among them human leucocyte antigen ( HLA ) has shown the strongest effect. However, studies on the functional contribution of HLA in controlling HIV progression toward AIDS are limited by multiple issues, including the viral strain variability within the study subjects. In this study, in a cohort of children infected with a monophyletic strain ( CRF 02_ AG ) during an outbreak, we evaluated the HIV ‐1 G ag, V if, V pr, T at and hepatitis C virus E 1/ E 2 (as control) proteins circulating in a cohort for the capability to be presented by the HLA molecules in the same population. A total of 70 Non‐progressors and 37 Progressors to AIDS were evaluated. In the presence of a constant capability of HIV ‐1 to mutate in the region containing epitopes of G ag protein, the number of epitopes recognized in silico by the combination of the HLA alleles along the Gag consensus sequence is significantly higher in the Non‐progressors compared with Progressors ( HLA ‐A: Non‐progressors = 1·532 ± 1·211, Progressors = 0·7714± 1·031, P = 0·0016; HLA ‐B: Non‐progressors = 1·556 ± 1·298, Progressors = 1·000 ± 0·817, P = 0·0319; HLA ‐ DR : Non‐progressors = 13·30± 9·488, Progressors = 7·294 ± 6·952, P = 0·0006). Similar results were obtained for the other HIV ‐1 proteins V if and V pr, whereas no differences were obtained in the number of epitopes for the hepatitis C virus E 1/ E 2 protein sequence or for the scrambled HIV ‐1 sequence. Finally, the results were confirmed also in a subgroup of subjects where both HLA typing and G ag sequence were available. In conclusion, in the absence of bias due to viral strain diversity, it is the overall fitting of the HLA molecules that are capable of better binding HIV ‐1 proteins in determining the major role in the control of HIV ‐1 replication and progression to AIDS .