Clinical Control of HIV-1 by Cytotoxic T Cells Specific for Multiple Conserved Epitopes.

Abstract

UNLABELLED:

Identification and characterization of CD8(+) T cells effectively controlling HIV-1 variants are necessary for the development of AIDS vaccines and for studies of AIDS pathogenesis, although such CD8(+) T cells have been only partially identified. In this study, we sought to identify CD8(+) T cells controlling HIV-1 variants in 401 Japanese individuals chronically infected with HIV-1 subtype B, in which protective alleles HLA-B*57 and HLA-B*27 are very rare, by using comprehensive and exhaustive methods. We identified 13 epitope-specific CD8(+) T cells controlling HIV-1 in Japanese individuals, though 9 of these epitopes were not previously reported. The breadths of the T cell responses to the 13 epitopes were inversely associated with plasma viral load (P = 2.2 × 10(-11)) and positively associated with CD4 count (P = 1.2 × 10(-11)), indicating strong synergistic effects of these T cells on HIV-1 control in vivo. Nine of these epitopes were conserved among HIV-1 subtype B-infected individuals, whereas three out of four nonconserved epitopes were cross-recognized by the specific T cells. These findings indicate that these 12 epitopes are strong candidates for antigens for an AIDS vaccine. The present study highlighted a strategy to identify CD8(+) T cells controlling HIV-1 and demonstrated effective control of HIV-1 by those specific for 12 conserved or cross-reactive epitopes.

IMPORTANCE:

HLA-B*27-restricted and HLA-B*57-restricted cytotoxic T lymphocytes (CTLs) play a key role in controlling HIV-1 in Caucasians and Africans, whereas it is unclear which CTLs control HIV-1 in Asian countries, where HLA-B*57 and HLA-B*27 are very rare. A recent study showed that HLA-B*67:01 and HLA-B*52:01-C*12:02 haplotypes were protective alleles in Japanese individuals, but it is unknown whether CTLs restricted by these alleles control HIV-1. In this study, we identified 13 CTLs controlling HIV-1 in Japan by using comprehensive and exhaustive methods. They included 5 HLA-B*52:01-restricted and 3 HLA-B*67:01-restricted CTLs, suggesting that these CTLs play a predominant role in HIV-1 control. The 13 CTLs showed synergistic effects on HIV-1 control. Twelve out of these 13 epitopes were recognized as conserved or cross-recognized ones. These findings strongly suggest that these 12 epitopes are candidates for antigens for AIDS vaccines.

• Authors: Hayato Murakoshi, Tomohiro Akahoshi, Madoka Koyanagi, Takayuki Chikata, Takuya Naruto, Rie Maruyama, Yoshiko Tamura, Naoki Ishizuka, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
• Journal: Journal of virology (J Virol) Vol. 89 Issue 10 Pg. 5330-9 (May 2015) ISSN: 1098-5514 [Electronic] United States
• PMID: 25741000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• AIDS Vaccines
• Epitopes, T-Lymphocyte
• HIV Antigens
• HLA-B Antigens
• HLA-B27 Antigen
• HLA-B57 antigen
• gag Gene Products, Human Immunodeficiency Virus
• nef Gene Products, Human Immunodeficiency Virus
• nef protein, Human immunodeficiency virus 1
• pol Gene Products, Human Immunodeficiency Virus

Topics

• AIDS Vaccines (genetics, immunology)
• Asian People (genetics)
• CD4 Lymphocyte Count
• Conserved Sequence
• Cross Reactions
• Epitopes, T-Lymphocyte (genetics, immunology)
• HIV Antigens (genetics)
• HIV Infections (genetics, immunology, virology)
• HIV-1 (genetics, immunology)
• HLA-B Antigens (genetics, immunology)
• HLA-B27 Antigen (genetics, immunology)
• Host-Pathogen Interactions (genetics, immunology)
• Humans
• Mutagenesis, Site-Directed
• T-Lymphocytes, Cytotoxic (immunology, virology)
• Viral Load
• gag Gene Products, Human Immunodeficiency Virus (genetics, immunology)
• nef Gene Products, Human Immunodeficiency Virus (genetics, immunology)
• pol Gene Products, Human Immunodeficiency Virus (genetics, immunology)