The Walker laboratory focuses on mechanisms of immune control in HIV infection, focusing in particular on persons who control HIV infection spontaneously without the need for medication. Through an international collaboration now funded by the Gates Foundation, more than 900 persons who control HIV infection to less than 2000 RNA Copies/ml without the need for antiviral medications have been recruited, and immunologic, virologic and host genetic mechanisms accounting for this remarkable phenotype are being investigated. At the same time, efforts are underway to define the subset of CD8 T cell responses that exert the strongest antiviral effect, and to define those responses that are simply passengers and fail to contribute to immune control. In addition to these efforts in Boston, a major effort is underway at our laboratory at the Nelson Mandela School of Medicine, where a major population based effort is underway to define evolution of clade C virus infection under immune selection pressure, and to define predictable pathways to immune escape. 

Present Areas of Investigation:
		Define the relative antiviral efficacy of epitope-specific CTL responses in infected persons
		Define the predicatable pathways to immune escape in infected persons
		Define the mechanisms that underlie effective cell killing
		Define the mechanisms of spontaneous control of HIV infection using a genome wide association scan.
Important Accomplishments:
		Identification of strong circulating HIV-specific cytotoxic T lymphocytes in infected persons.
		Identification of HIV-specific CD4 T cells and their association with immune control of HIV.
		Identification of immunoregulatory pathways that turn HIV-specific immune responses off in vivo.
		Demonstration of the superior antiviral efficacy of Gag-specific CD8 T cell responses.
Publications of Interest:
	1.	Draenert R, Allen T, Yang L, Wrin T, Chappey C, Verrill C, Guillem S, Eldridge R, Lahaie M, Ruiz L, Bonaventura C, Petropoulos C, Walker B, Martinze-Picado J. Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus. JEM. 2006 Mar 20; 203 (3): 529-39.
	2.	Day C.L., Kaufmann D.E., Kiepiela P., Brown JA., Moodley ES., Reddy S., Mackey EW., Miller J.D., Leslie A.J., DePierres C., Mncube Z., Duraiswamy J., Zhu B., Eichbaum Q., Altfeld M., Wherry E.J., Coovadia H.M., Goulder P.J., Klenerman P., Ahmed R., Freeman GJ., Walker B.D. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006 Sep 21;443(7109):350-4.
	3.	Altfeld M, Kalife ET, Qi Y, Streeck H, Lichterfeld M, Johnston MN, Burgett N, Swartz ME, Yang A, Alter G, Yu XG, Meier A, Rockstroh JK, Allen TM, Jessen H, Rosenberg ES, Carrington M, Walker BD. HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8(+) T Cell Response against HIV-1. PLoS Med. 2006 Oct;3(10):e403.
	4.	Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, Reddy S, de Pierres C, Mncube Z, Mkhwanazi N, Bishop K, van der Stok M, Nair K, Khan N, Crawford H, Payne R, Leslie A, Prado J, Prendergast A, Frater J, McCarthy N, Brander C, Learn GH, Nickle D, Rousseau C, Coovadia H, Mullins JI, Heckerman D, Walker BD, Goulder P. CD8(+) T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med. 2007 Jan;13(1):46-53. Epub 2006 Dec 17.
	5.	Yu XG, Lichterfeld M, Williams KL, Martinez-Picado J, Walker BD. Random TCR recruitment in HIV-1-specific CD8+ T cells from genetically identical twins infected with the same HIV-1 strain. J Virol. 2007 Sep 5.
	6.	Kaufmann, D. E., D. G. Kavanagh, et al. (2007). "Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction." Nat Immunol 8(11): 1246-54.
	7.	Kaufmann, D. E., D. G. Kavanagh, et al. (2007). "Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction." Nat Immunol 8(11): 1246-54.