To this end, our research program focuses on major viral mechanisms of resistance to the cell-mediated immune (CMI) response, which normally eradicates infected cells by direct lysis. To maintain a chronic infection HIV must evade lysis by both cytotoxic T lymphocytes (CTLs), and natural killer (NK) cells. CTLs recognize infected cells with receptors that detect foreign peptide antigens presented in association with host major histocompatibility class I protein (MHC-I). NK cells recognize cells with abnormally low MHC-I levels and/or those that have upregulated NK activating ligands. Our goals are to better understand viral mechanisms of immune evasion and to ultimately inhibit these processes.
Collins, K.L., Chen, B.K., Kalams , S.A. , Walker , B.D., Baltimore, D. (1998). The HIV-1 Nef protein protects infected primary human cells from CTLs. Nature, 391:397-401.
Williams, M., Roethe, J., Kasper, M.R., Fleis, R., Przybycin, C.G., Collins, K.L., (2002) Direct binding of HIV-1 Nef to the MHC-I cytoplasmic tail disrupts MHC-I trafficking, J. Virol., 76 (23); 12173-12184.
Bobbitt, K.R., Addo, M.M, Altfeld, M., Filzen, T., Onafuwa, A.A., Walker, B.D. and Collins, K.L., (2003) Rev activity determines sensitivity of HIV-infected primary T cells to anti-Gag CTL killing, Immunity, 18 (2) 289-299. (highlighted in Nature Reviews Immunology 3, (2003;266-267).
Roeth, J.F., Kasper, M.R., Williams, M., Filzen, T.F., and Collins, K. L., (2004) HIV-1 Nef re-directs MHC-I from the TGN to lysosomes by stabilizing an interaction between MHC-I and AP-1. J Cell Biol. 167(5); 903-913.
Williams, M., Roeth, J.F., and Collins, K.L., (2005) HIV-1 Nef domains required for disruption of MHC-I trafficking are also necessary for co-precipitation of Nef with HLA-A2. J Virol. 79(1);632-636.
Kasper, M.R., Williams, M., Xie, D., Fleis, R. and Collins, K.L., (2005) HIV-1 Nef disrupts viral antigen presentation early in the secretory pathway by preferentially binding hypo-phosphorylated MHC-I cytoplasmic tails. J Biol Chem. 280(13): 12840-12848.
Wonderlich ER, Williams M, Collins KL. The tyrosine binding pocket in the adaptor protein 1 (AP-1) mu1 subunit is necessary for Nef to recruit AP-1 to the major histocompatibility complex class I cytoplasmic tail. J Biol Chem. 2008 Feb 8;283(6):3011-22.
Leonard, J.A., Filzen,T., Carter, C.C., Schaefer, M., Collins,K.L., (2011)
Norman, J.M., McNamara, L.A., Onafuwa-Nuga, Mashiba, M., Chiari,E. and Collins K.L., (2011) HIV-1 Vif and Nef limit natural killer cell recognition of infected primary T cells by restricting Vpr-dependent NKG2D upregulation, Nature Immunology, In Press.