A Novel Immunodominant CD8+ T Cell Response Restricted by a Common HLA-C Allele Targets a Conserved Region of Gag HIV-1 Clade CRF01_AE Infected Thais

• Published in: PloS one Vol. 6; no. 8; p. e23603
• Main Authors: Buranapraditkun, Supranee, Hempel, Ursula, Pitakpolrat, Patrawadee, Allgaier, Rachel L., Thantivorasit, Pattarawat, Lorenzen, Sven-Iver, Sirivichayakul, Sunee, Hildebrand, William H., Altfeld, Marcus, Brander, Christian, Walker, Bruce D., Phanuphak, Praphan, Hansasuta, Pokrath, Rowland-Jones, Sarah L., Allen, Todd M., Ruxrungtham, Kiat
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.08.2011; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; AIDS vaccines; Alleles; Amino Acid Sequence; Antigenic determinants; Biology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Conserved Sequence - genetics; Control; Cytotoxicity; Development and progression; Drug resistance; Enzyme-linked immunosorbent assay; Epidemiology; Epitopes; Female; gag Gene Products, Human Immunodeficiency Virus - chemistry; gag Gene Products, Human Immunodeficiency Virus - immunology; Glycoproteins; Health aspects; Histocompatibility antigen HLA; HIV; HIV Infections - genetics; HIV Infections - immunology; HIV tests; HIV-1; HLA antigens; HLA-C Antigens - genetics; Human immunodeficiency virus; Humans; Immunodominant Epitopes - chemistry; Immunodominant Epitopes - immunology; Immunology; Immunopathogenesis; Infection; Infections; Interferon; Laboratories; Lymphocytes; Lymphocytes T; Male; Medical research; Medicine; Molecular Sequence Data; Mutation - genetics; Peptides; Proteins; Regional development; T cells; Thailand; Trends; Vaccines; Thailand; Asia; United States > US; Massachusetts; Oklahoma; Bangkok Thailand
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0023603

CD8+ T cell responses play an important role in the control of HIV-1. The extensive sequence diversity of HIV-1 represents a critical hurdle to developing an effective HIV-1 vaccine, and it is likely that regional-specific vaccine strains will be required to overcome the diversity of the different HIV-1 clades distributed world-wide. Unfortunately, little is known about the CD8+ T cell responses against CRF01_AE, which is responsible for the majority of infections in Southeast Asia. To identify dominant CD8+ T cell responses recognized in HIV-1 clade CRF01_AE infected subjects we drew upon data from an immunological screen of 100 HIV-1 clade CRF01_AE infected subjects using IFN-gamma ELISpot to characterize a novel immunodominant CD8+ T cell response in HIV-1 Gag restricted by HLA-Cw*0102 (p24, (277)YSPVSILDI(285), YI9). Over 75% of Cw*0102+ve subjects targeted this epitope, representing the strongest response in more than a third of these individuals. This novel CD8 epitope was located in a highly conserved region of HIV-1 Gag known to contain immunodominant CD8 epitopes, which are restricted by HLA-B*57 and -B*27 in clade B infection. Nonetheless, viral escape in this epitope was frequently observed in Cw*0102+ve subjects, suggestive of strong selection pressure being exerted by this common CD8+ T cell response. As HLA-Cw*0102 is frequently expressed in the Thai population (allelic frequency of 16.8%), this immunodominant Cw*0102-restricted Gag epitope may represent an attractive candidate for vaccines specific to CRF01_AE and may help facilitate further studies of immunopathogenesis in this understudied HIV-1 clade.