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

作者：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

来源：PLos One, 2011, 6(8): e23603.

DOI：10.1371/journal.pone.0023603

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.
Methodology/Principal Findings: 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 IFNgamma 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/Significance: 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.

• 出版日期2011-8-22