Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition

Abstract

In a longitudinal study of HIV seropositive patients, there were fluctuations in the specificity of cytotoxic T cells for the virus. This was matched by variability in proviral gag DNA epitope sequences in the lymphocytes of these patients. Some of these viral variants are not recognized by autologous T cells. Accumulation of such mutations in T-cell antigenic targets would provide a mechanism for immune escape.

Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA‐B*2705

“…Indeed HIV has been shown to escape from CTL immune surveillance by mutation at P2 [3,30], and this escape is mediated by immune selection pressure [31,32]. The viral capsid interactions between two neighboring p24 molecules are mediated by residues within the HIV epitope, and it appears that modification of the P6 leucine to methionine permits mutation of the P2 arginine without significant loss of viral fitness [31].…”

“…Studies have shown that the M6 mutant retains full binding potential to the HLA-B*2705 groove [30,31], and the HLA-B*2705-HIV structure indicates that the P6 leucine side chain, being solvent-exposed, plays little role in stabilizing the HIV epitope's binding to HLA-B*2705. We predict the mutation of P6L to methionine would have little overall impact on the peptide conformation, as there is ample space to accommodate a slightly bulkier methionine side chain.…”

CD8 + T Cell Breadth and Ex Vivo Virus Inhibition Capacity Distinguish between Viremic Controllers with and without Protective HLA Class I Alleles

“…However, virusspecific CD8 ϩ T cell immune responses are not equally effective in HIV control, as the majority of infected individuals progress to disease despite the presence of these cells. HIV is able to evade immune responses by developing mutations that mediate escape from CTL recognition (6)(7)(8)(9)(10)(11)(12). In addition, the expression of certain HLA class I molecules by HIV-infected patients, such as HLA-B*27, HLA-B*57, HLA-B*58:01, HLA-B*81:01, and HLA-A*74: 01, is associated with better clinical disease outcomes in some population settings (3,(13)(14)(15)(16)(17)(18).…”

Cellular Immune Recognition and the Biological Role of Major Transplantation Antigens

“…escaped the T-cell response has subsequently also been found in patients infected with HIV by R. Phillips, A. McMichael and coworkers [93] and in HBV-infected patients by Bertoletti et al [94].…”