Human congenital T-cell receptor disorders

Abstract

Immunodeficiencies of most T-cell receptor (TCR) components (TCRID) have been reported in almost 40 patients worldwide who have also, at times, shown signs of autoimmunity. We updated their clinical, immunological, and molecular features with an emphasis on practical diagnosis, as the range of the disorder grows in complexity with new partial defects. Cellular and animal models are also reviewed and in some cases reveal their limitations for predicting TCRID immunopathology.

γδ T Lymphocytes in the Diagnosis of Human T Cell Receptor Immunodeficiencies

“…Surface γδTCR expression was also reduced (4% vs. healthy controls, Figure 1 B). The number of αβ T cells was only slightly reduced despite their similarly reduced surface TCR, with all reported cases showing reduced numbers of CD4 + T cells but normal or high numbers of CD8 + T cells ( 21 , 25 – 27 ).…”

“…CD3γ deficient patients, most of which showed mild ID ( 21 ), had normal numbers of polyclonal peripheral blood γδ T cells [absolute and relative, ( 22 ) and Figure 1 A] with low surface TCR [around 30% of control levels ( 22 ) and Figure 1 B], similarly to their αβ T cell counterparts ( 23 ), likely with an abnormal γδTCR/δεδεζζ stoichiometry. Despite their high homology, the invariant CD3γ and δ chains show different roles in human vs. mouse γδ T cell development.…”

“…γδ T cells were studied in only two of three reported CD247 deficient patients ( 21 ). The patients showed SCID features and reduced absolute and relative γδ T cells numbers (Figure 1 A).…”

Primary T-cell immunodeficiency with functional revertant somatic mosaicism in CD247

“…4 Thus, the presence of revertants along with strongly reduced surface TCR expression is pathognomonic of CD247 deficiency. 5,6 The new case described here showed complete CD247 protein deficiency due to loss of the initiation codon. The disorder was associated with strongly reduced surface TCR and multiple developmental and functional T-cell derangements, suggesting that, as observed in mice, 7 CD247 plays a critical role for T-cell selection in the thymus.…”

2014 Joint Immunodeficiency Canada/Israel Association of Allergy and Clinical Immunology SymposiumDecember 4, 2014Dan Carmel HotelHaifa, Israel

“…TCR isotypes in mature T cells. Chains for which mutations have been reported to cause immunodeficiency and/or autoimmunity(Table 1)are depicted in red(Marin et al 2014) …”