The rockefeller university

Event Details

Type

Friday Lecture Series

Speaker(s)

Bruce Walker, M.D., principal investigator, Ragon Institute of MGH, MIT and Harvard

Speaker bio(s)

A small percentage (<1%) of persons infected with HIV are able to durably control virus replication in the absenece of therapy. The strongest association with such control is expression of certain human leukocyte antigen (HLA) class I alleles, yet the majority of persons expressing these alleles experience progressive infection. Here Dr. Walker's lab undertook a study to define the genetic and immunologic basis for the HLA protective effect. Through a genome wide association scan and subsequent amino acid analysis of the major SNP signal, which was confined to the MHC region, they show that specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles, indicating that the nature of the nature of the HLA-peptide interaction is the major genetic factor modulating control. By extending these studies in conducting a comparative quantitative and qualitative analyses of the immunodominant HIV-1 specific CD8+ T cell responses in HIV-1 controllers and progressors expressing the protective alleles, Dr. Walker's team shows that control vs progression is further defined by distinct TCR clonotypes with more germline-like TCRB CDR3 sequences in controllers compared to progressors, which are characterized by superior control of replication of HIV-1 in vitro and greater cross-reactivity against epitope variants, and that this maps to specific differences in killing function at a the level of the TCR clonotype. These data indicate that the efficacy of protective alleles is modulated by specific TCR clonotypes, provide an explanation for divergent HIV-1 outcomes in persons with protective HLA alleles, and have important implications for therapeutic and prophylactic vaccines.

Dr. Walker is a professor of medicine at Harvard Medical School, a Howard Hughes Medical Institute investigator, and director of the Ragon Institute of MGH, MIT and Harvard. In addition to his clinical duties as a board certified infectious disease specialist, his research focuses on cellular immune responses in chronic viral infections, with a particular focus on HIV. He leads an international translational clinical and basic science research effort to understand how some rare people who are infected with HIV, but have never been treated, can fight the virus with their immune system.

Dr. Walker is also an adjunct professor at the Nelson Mandela School of Medicine in Durban. There he collaborates with the Doris Duke Medical Research Institute at the University of KwaZulu-Natal and serves as a principal investigator in the HIV Pathogenesis Program, an initiative to study the evolution of the HIV and the immune responses effective in controlling this virus, as well as to contribute to training the next generation of African scientists. Recently he has become a member of the Steering Committee for the KwaZulu-Natal Research Institute for TB and HIV (K-RITH), a 10 year initiative funded by HHMI to build a state of the art TB-HIV research facility at the heart of these dual epidemics in South Africa.

Dr. Walker is a member of the American Academy of Arts and Sciences, American Society for Clinical Investigation (ASCI), the American Association of Physicians (AAP), and the Institute of Medicine (IOM) of the National Academy of Sciences.

Open to

Public

Host

Michel Nussenzweig

Reception

Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge

Contact

Robert Houghtaling

Phone

(212) 327-8072

Sponsor

Robert Houghtaling
(212) 327-8072
rhoughtali@rockefeller.edu