The Ragon Institute of MGH, MIT and Harvard

Adaptive Immunity

An expanding body of evidence demonstrates that the adaptive immune response is able to control HIV-1 replication in infected individuals.

Studies of AIDS virus infection in animal models and humans have indicated a dominant role for CD8+ T cells in controlling HIV replication and influencing viral set point, and the need for virus-specific T helper cells to maintain and coordinate these responses.

The antiviral activity of specific CD8+ T cell responses in HIV-1 infection is inferred by a number of important observations, including

	(i) the significant association of specific HLA class I alleles with slower HIV-1 disease progression,
	(ii) the increased viral replication in SIV infected macaques following the depletion of CD8+ (NK and T) cells,
	(iii) the rapid emergence of CD8+ T cell escape mutations within targeted epitopes,
	(iv) the adaptation of HIV-1 to HLA class I restricted T cell responses on the population level,
	and (v) the decrease of SIV replication in macaques that were immunized with vaccines inducing strong SIV-specific CD8+ T cell responses prior to SIV challenge.

Together these data indicate strong selection pressure applied by the CD8+ T cell response on HIV-1 that can result in a reduction of viral replication.

However, these studies have also demonstrated that not all virus-specific T cell responses are created equally, as strong HIV-1-specific CD8+ T cell responses are observed in individuals with rapidly progressing HIV-1 disease. Very little is known about the characteristics of those CD8+ T cell responses that mediate protective immunity in HIV-1 infection.

Several groups at the Ragon Institute are involved in research efforts aimed at identifying the characteristics of protective T cell responses against HIV-1, and to translate those findings into the design of protective HIV-1 vaccines.

Laboratories which focus on Adaptive Immunity:
		Altfeld Lab
		Le Gall Lab
		Walker Lab
		Yu Lab