323 Differences in the Expressed HLA Class I Alleles Determine the Differential Clustering of HIV-1-Specific T-cell Responses in Infected Chinese and Caucasians X. G. Yu*1, B. Perkins1, M. M. Addo1, F. Wei2, A. Rathod1, M. Parta3, P. Lee1, C. Adams1, A. Wurcel1, N. Frahm1, E. S. Rosenberg1, C. Brander1, Y. Cao2, B. D. Walker1, M. Altfeld1 1Partners AIDS Res Ctr, Mass Gen Hosp /Div of AIDS, Harvard Med Sch, Boston, MA; 2Chinese Academy of Preventive Med, Beijing, China; and 3Belvue Hosp, New York, NY
Background: China is estimated to have one of the world’s most rapidly spreading HIV-1 epidemics. Studies providing insights into HIV-1 pathogenesis in infected Chinese are urgently needed to design and test an effective HIV-1 vaccine that prevents infection or attenuates disease in this population.
Methods: HIV-1 specific T-cell responses were characterized in 32 HIV-1 infected Chinese and 45 infected Caucasians using 410 overlapping peptides (18mers with 10aa overlap) spanning the entire HIV-1 clade B consensus sequence in an IFN-gamma ELISpot assay. HLA class I typing for both cohorts was determined by sequence-specific primer PCR. The frequency by which the different overlapping peptides were targeted in the 2 populations was calculated throughout the genome and regions targeted by more than 15% of tested individuals were defined as "clusters" of T-cell responses. The infecting HIV-1 clade in the Chinese subjects was determined by HMA.
Results: The predominant HLA class I alleles in studied Chinese were HLA-A11 (38%), A2 (24%), A24 (15%) and B60 (29%), while HLA-A2 (28%), A3 (15%), B44 (14%) and B7 (11%) were the predominant alleles in Caucasians. HIV-1-specific T-cell responses were clustering in 15 different regions of the HIV-1 genome in the studied Chinese and in 22 different regions in the studied Caucasians, with 5 regions frequently targeted by both populations. Described optimal CD8+ T-cell epitopes corresponding to the dominant HLA class I alleles expressed in the 2 populations were located in the regions of the HIV-1 genome that were frequently targeted by the respective populations. While HIV-1 clade B was the predominant clade in infected Caucasians, HIV-1 clade CRF01_AE, B and C were present in the infected Chinese. A large degree of cross-recognition of clade B peptides in individuals infected with diverse HIV-1 clades was observed.
Conclusions: These data demonstrate differences as well as homologies in the regions of HIV-1 targeted by CD8+ T-cells of infected Chinese and Caucasians. The differential clustering of virus-specific T-cell responses was mainly due to differences in the genetic HLA class I background in these populations. The design of an effective vaccine to fight the rapidly growing HIV-1 epidemic in China must take these HLA-class-I differences as well as differences in the infecting viral clades into account.
