Longitudinal analysis of T cell receptor (TCR) gene usage by human immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals a limited TCR repertoire.

Human immunodeficiency virus 1 (HIV-1) infection is associated with a vigorous cellular immune response that allows detection of cytotoxic T lymphocyte (CTL) activity using freshly isolated peripheral blood mononuclear cells (PBMC). Although restricting class I antigens and epitopes recognized by HIV-1-specific CTL have been defined, the effector cells mediating this vigorous response have been characterized less well. Specifically, no studies have addressed the breadth and duration of response to a defined epitope. In the present study, a longitudinal analysis of T cell receptor (TCR) gene usage by CTL clones was performed in a seropositive person using TCR gene sequences as a means of tracking responses to a well-defined epitope in the glycoprotein 41 transmembrane protein. 10 CTL clones specific for this human histocompatibility leukocyte antigen-B14-restricted epitope were isolated at multiple time points over a 31-mo period. All clones were derived from a single asymptomatic HIV-1-infected individual with a vigorous response to this epitope that was detectable using unstimulated PBMC. Polymerase chain reaction amplification using V alpha and V beta family-specific primers was performed on each clone, followed by DNA sequencing of the V-D-J regions. All 10 clones utilized V alpha 14 and V beta 4 genes. Sequence analysis of the TCR revealed the first nine clones isolated to also be identical at the nucleotide level. The TCR-alpha junctional region sequence of the tenth clone was identical to the junctional region sequences of the other nine, but this clone utilized distinct D beta and J beta gene segments. This study provides evidence that the observed high degree of HIV-1-specific CTL activity may be due to monoclonal or oligoclonal expansion of specific effector cells, and that progeny of a particular CTL clone may persist for prolonged periods in vivo in the presence of a chronic productive viral infection. The observed limited TCR diversity against an immunodominant epitope may limit recognition of virus variants with mutations in regions interacting with the TCR, thereby facilitating immune escape.

Cluster and principal component analysis for Kováts' retention indices on apolar and polar stationary phases in gas chromatography.

An extended set of Kováts' retention indices of 137 organic compounds obtained at 405.15K with C 78 standard alkane and with standalone polar interactive groups was analyzed. The retention data determined using gas chromatography were subjected to hierarchical cluster analysis and principal component analysis to detect structure in the data and to classify retention indices and solutes alike. The statistical evaluation of the retention data explored the correlation between the retention indices of the solutes and the similarities/differences of the stationary liquids. A set of chromatographic systems was selected as possible new standards relating to linear solvation energy relationships based on the chemometric data reduction. The new molecular descriptors based on retention indices were tested in correlation models for normal boiling point and olive oil/gas partition coefficient data using ridge regression. The ridge regression provided new ways for variable selection. The normal boiling points of organic compounds can reasonably be described using retention indices on apolar (C78) and polar (trifluoro, hydroxy, bromo and cyano) model compounds. The partition coefficients between olive oil and the gas phase can similarly be well correlated with retention indices on apolar (C78) and polar (tetramethoxy, trifluoro and hydroxy) model compounds.