Escape mutation selected by Gag28-36-specific cytotoxic T cells in HLA-A*2402-positive HIV-1-infected donors |
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| Institution: | 1. Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan;2. Division of Infectious Disease, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan;3. AIDS Clinical Center, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan;1. Fisher College of Business, The Ohio State University, 524 Fisher Hall, Columbus, OH 43210, United States;2. Fisher College of Business, The Ohio State University, 356 Fisher Hall, Columbus, OH 43210, United States;3. Arkansas State University, College of Business, United States;1. Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina;2. Department of Ophthalmology, Associated Retina Consultants, Royal Oak, Michigan;1. Department of Physics, Stockholm University, Albanova University Center, SE-106 91 Stockholm, Sweden;2. Microsoft Station Q, University of California, Santa Barbara, CA 93106-6105, USA;3. Department of Mathematics, Texas A&M University, College Station, TX 77843, USA;4. Microsoft Station Q and Dept of Mathematics, University of California, Santa Barbara, CA 93106-6105, USA;1. Department of Microbiology, Ponce School of Medicine and Health Sciences, Ponce, PR 00716, USA;2. Department of Biochemistry, Ponce School of Medicine and Health Sciences, Ponce, PR 00716, USA;3. Division of Pharmacology, School of Pharmacy, University of Missouri, Kansas City, MO 64108, USA;1. Australian Future Fibres Research & Innovation Centre, Institute for Frontier Materials, Deakin University, VIC 3217, Australia;2. Sir Lawrence Wackett Aerospace Research Centre, School of Aerospace, Mechanical & Manufacturing Engineering, RMIT University, VIC 3283, Australia;3. School of Textile Science and Engineering, Wuhan Textile University, Wuhan 430073, China |
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| Abstract: | Gag-specific CTLs are known to have stronger ability to control HIV-1 replication than others that are protein-specific. Therefore, the analysis of Gag escape mutants is expected to clarify the mechanisms of immune control in HIV-1-infected donors. However, only a limited number of Gag escape mutants have been identified so far. A previous study suggested the possibility that Gag28-3R (KW9-3R) is an escape mutant from HLA-A*2402-restricted KW9-specific CTLs but did not show any evidence of it. Here we sought to demonstrate that KW9-3R is selected as escape mutant by KW9-specific CTLs. KW9-specific CTLs showed a remarkable reduction in recognition of target cells infected with the KW9-3R mutant. The sequence analysis of HIV-1 from 58 HIV-1-infected individuals showed that the frequency of the KW9-3R mutant was significantly higher in HLA-A*2402+ individuals than in HLA-A*2402− individuals. Longitudinal analysis of an HLA-A*2402+ individual with HIV-1 early infection showed that this escape mutant was selected over an approximately 2-year period. These results together indicate that Gag28-3R is an escape mutant selected by HLA-A*2402-restricted KW9-specific CTLs. Further analysis of this epitope will clarify the role of HIV-1-specific CTLs in the control of HIV-1 among the Japanese population, since 70% of them carry this allele. |
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