title: 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.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Vaccine and Cellular Immunology Laboratory, Chulalongkorn Medical Research Center (ChulaMRC), and Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors: Supranee
authors: S
authors: Buranapraditkun
authors: Ursula
authors: U
authors: Hempel
authors: Patrawadee
authors: P
authors: Pitakpolrat
authors: Rachel L
authors: RL
authors: Allgaier
authors: Pattarawat
authors: P
authors: Thantivorasit
authors: Sven-Iver
authors: SI
authors: Lorenzen
authors: Sunee
authors: S
authors: Sirivichayakul
authors: William H
authors: WH
authors: Hildebrand
authors: Marcus
authors: M
authors: Altfeld
authors: Christian
authors: C
authors: Brander
authors: Bruce D
authors: BD
authors: Walker
authors: Praphan
authors: P
authors: Phanuphak
authors: Pokrath
authors: P
authors: Hansasuta
authors: Sarah L
authors: SL
authors: Rowland-Jones
authors: Todd M
authors: TM
authors: Allen
authors: Kiat
authors: K
authors: Ruxrungtham
mesh_terms: D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017124:Conserved Sequence / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D013785:Thailand; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology*
chemical_list: D015236:HLA-C Antigens; D016056:Immunodominant Epitopes; D054301:gag Gene Products, Human Immunodeficiency Virus