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Analysis of the CD8 + T cell anti-HIV activity in heterologous cell co-cultures reveals the benefit of multiple HLA class I matches.
- Source :
-
Immunogenetics [Immunogenetics] 2018 Feb; Vol. 70 (2), pp. 99-113. Date of Electronic Publication: 2017 Jul 22. - Publication Year :
- 2018
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Abstract
- CD8 <superscript>+</superscript> T lymphocytes can reduce the production of human immunodeficiency virus 1 (HIV-1) by CD4 <superscript>+</superscript> 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 <superscript>+</superscript> T cells, isolated from the peripheral blood of HIV-1-infected individuals, with panels of autologous and heterologous acutely HIV-1-infected primary CD4 <superscript>+</superscript> T cells. Altogether, CD8 <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> 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 <superscript>+</superscript> T cell anti-HIV activity than supertype pairings. Antibodies against HLA class I and CD3 reduced the CD8 <superscript>+</superscript> T cell anti-HIV activity. Stimulated CD8 <superscript>+</superscript> 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 <superscript>+</superscript> 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.
- Subjects :
- CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Coculture Techniques methods
Genes, MHC Class I immunology
HIV Infections virology
HIV-1 immunology
HLA-B Antigens genetics
HLA-C Antigens genetics
Humans
Primary Cell Culture
Virus Replication
CD8-Positive T-Lymphocytes physiology
Histocompatibility Antigens Class I genetics
Histocompatibility Antigens Class I immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1432-1211
- Volume :
- 70
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Immunogenetics
- Publication Type :
- Academic Journal
- Accession number :
- 28735348
- Full Text :
- https://doi.org/10.1007/s00251-017-1021-7