Homozygous Human TAP Peptide Transporter Mutation in HLA Class I Deficiency

Abstract

Human lymphocyte antigen (HLA) class I proteins of the major histocompatibility complex are largely dependent for expression on small peptides supplied to them by transporter associated with antigen processing (TAP) protein. An inherited human deficiency in the TAP transporter was identified in two siblings suffering from recurrent respiratory bacterial infections. The expression on the cell surface of class I proteins was very low, whereas that of CD1a was normal, and the cytotoxicity of natural killer cells was affected. In addition, CD8+ alpha beta T cells were present in low but significant numbers and were cytotoxic in the most severely affected sibling, who also showed an increase in CD4+CD8+ T cells and gamma delta T cells.

CD1d-Specific NK1.1+ T Cells with a Transgenic Variant TCR

“…VIII24 belongs to a set of CD1d-reactive hybridomas generated from CD4 ϩ T cells from MHC class II-deficient mice, which were shown to respond to CD1d in the absence of added Ags (7). The reactivity of VIII24 was dependent on the expression by the APC of ␤ 2 -microglobulin (␤ 2 m), but not the TAP molecule (7), consistent with the requirements for CD1d expression (32)(33)(34). Stimulation could be inhibited by Abs to CD1d, or to either of the TCR V-segments, V␣3.2 or V␤9 (S. Cardell, unpublished data).…”

HLA class I deficiencies due to mutations in subunit 1 of the peptide transporter TAP1

“…In two cases chronic skin ulcers were reported (5, 6), while in a third case general vasculitis was observed (7). In three cases, the HLA class I deficiency has been shown to result from the absence of a functional TAP2 subunit (7,8). This report describes the genetic defects of two other HLA class I-deficient patients presenting cutaneous lesions (5,6,9).…”

“…Among these patients, three have been found to have TAP2 deficiency (7,8). In this work, we analyzed the genetic defects of two other patients.…”

“…However, we have previously shown in two TAP2 -deficient patients that numbers of CD8 + αβ T cells are generally low and normal ratios of CD8 + to CD4 + cells can result from a sharp expansion of γδ T cells, one third of them being CD8 + (8). Additional studies will thus be necessary to investigate more precisely the T cell populations in patient 2, a 46-year-old who is still alive but no longer followed by one of our teams.…”

“…They were treated or not either with neuraminidase (Sigma Chemical Co.), in which case they were then analyzed by isoelectric focusing gel electrophoresis (IEF), or with Endoglycosidase H (Endo H) (New England Biolabs, Inc., Beverly, Massachusetts, USA), in which case they were then analysed by SDS-PAGE, as previously described (8).…”