PMID- 28735348 OWN - NLM STAT- MEDLINE DCOM- 20180827 LR - 20181113 IS - 1432-1211 (Electronic) IS - 0093-7711 (Linking) VI - 70 IP - 2 DP - 2018 Feb TI - Analysis of the CD8(+) T cell anti-HIV activity in heterologous cell co-cultures reveals the benefit of multiple HLA class I matches. PG - 99-113 LID - 10.1007/s00251-017-1021-7 [doi] AB - CD8(+) T lymphocytes can reduce the production of human immunodeficiency virus 1 (HIV-1) by CD4(+) T cells by cytotoxic and non-cytotoxic mechanisms. To investigate the involvement of human leukocyte antigen (HLA) class I compatibility in anti-HIV responses, we co-cultured primary CD8(+) T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4(+) T cells. Altogether, CD8(+) T cell anti-HIV activity was evaluated in more than 200 co-cultures. Marked heterogeneity in HIV-1 replication levels was observed among the co-cultures sharing a common CD8(+) T cell source. The co-cultures that exhibited greater than 50% reduction in HIV production were found to have significantly increased numbers of matching HLA class I alleles (Yates chi-square = 54.21; p < 0.001). With CD8(+) T cells from HIV controllers and asymptomatic viremic individuals, matching HLA-B and/or HLA-C alleles were more predictive of strong anti-HIV activity than matching HLA-A alleles. Overall, HLA class I genotype matches were more closely associated with CD8(+) T cell anti-HIV activity than supertype pairings. Antibodies against HLA class I and CD3 reduced the CD8(+) T cell anti-HIV activity. Stimulated CD8(+) T cells exhibited increased anti-HIV activity and reduced dependency on HLA compatibility. These findings provide evidence that the maximal suppression of HIV replication by CD8(+) T cells requires the recognition of multiple epitopes. These studies provide insight for HIV vaccine development, and the analytic approach can be useful for the functional characterization of HLA class I alleles and tentative HLA class I supertypes. FAU - Killian, M Scott AU - Killian MS AUID- ORCID: 0000-0002-2012-3732 AD - Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, 414 E. Clark St, Vermillion, SD, 57069, USA. m.scott.killian@gmail.com. AD - Department of Public Health, School of Health Sciences, University of South Dakota, Vermillion, SD, 57069, USA. m.scott.killian@gmail.com. FAU - Teque, Fernando AU - Teque F AD - Department of Medicine, University of California San Francisco, San Francisco, CA, 94143, USA. FAU - Sudhagoni, Ramu AU - Sudhagoni R AD - Department of Public Health, School of Health Sciences, University of South Dakota, Vermillion, SD, 57069, USA. LA - eng GR - ID09-SF-058/California HIV/AIDS Research Program/International GR - 3P30AI027763-19S2/National Institute of Allergy and Infectious Diseases/International PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20170722 PL - United States TA - Immunogenetics JT - Immunogenetics JID - 0420404 RN - 0 (HLA-B Antigens) RN - 0 (HLA-C Antigens) RN - 0 (Histocompatibility Antigens Class I) SB - IM MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology/*physiology MH - Coculture Techniques/methods MH - Genes, MHC Class I/immunology MH - HIV Infections/virology MH - HIV-1/immunology MH - HLA-B Antigens/genetics MH - HLA-C Antigens/genetics MH - Histocompatibility Antigens Class I/*genetics/*immunology MH - Humans MH - Primary Cell Culture MH - Virus Replication OTO - NOTNLM OT - Antiviral immunity OT - CD8+ T cells OT - Elite controllers OT - HIV-1 OT - HLA class I OT - Supertype EDAT- 2017/07/25 06:00 MHDA- 2018/08/28 06:00 CRDT- 2017/07/24 06:00 PHST- 2017/05/23 00:00 [received] PHST- 2017/07/17 00:00 [accepted] PHST- 2017/07/25 06:00 [pubmed] PHST- 2018/08/28 06:00 [medline] PHST- 2017/07/24 06:00 [entrez] AID - 10.1007/s00251-017-1021-7 [pii] AID - 10.1007/s00251-017-1021-7 [doi] PST - ppublish SO - Immunogenetics. 2018 Feb;70(2):99-113. doi: 10.1007/s00251-017-1021-7. Epub 2017 Jul 22.