The somatically generated T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

ABSTRACTMature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.

Download Full-text

The somatically generated portion of T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

eLife ◽

10.7554/elife.30918 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 12

Author(s):

Philippa Marrack ◽

Sai Harsha Krovi ◽

Daniel Silberman ◽

Janice White ◽

Eleanor Kushnir ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

T Cell ◽

Positive Selection ◽

T Cell Receptor ◽

T Cell Receptors ◽

Cell Receptor ◽

Structural Basis ◽

Major Histocompatibility ◽

Cell Receptors ◽

Histocompatibility Complex

Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.

Download Full-text

Peripheral T Cell Survival Requires Continual Ligation of the T Cell Receptor to Major Histocompatibility Complex–Encoded Molecules

Journal of Experimental Medicine ◽

10.1084/jem.186.8.1269 ◽

1997 ◽

Vol 186 (8) ◽

pp. 1269-1275 ◽

Cited By ~ 306

Author(s):

Jörg Kirberg ◽

Anton Berns ◽

Harald von Boehmer

Keyword(s):

T Cells ◽

Major Histocompatibility Complex ◽

T Cell ◽

Positive Selection ◽

T Cell Receptor ◽

Cell Receptor ◽

Major Histocompatibility ◽

Continuous Contact ◽

Mhc Molecules ◽

Histocompatibility Complex

In the thymus, T cells are selected according to their T cell receptor (TCR) specificity. After positive selection, mature cells are exported from primary lymphoid organs to seed the secondary lymphoid tissue. An important question is whether survival of mature T cells is an intrinsic property or requires continuous survival signals, i.e., engagement of the TCR by major histocompatibility complex (MHC) molecules in the periphery, perhaps in a similar way as occurring during thymic positive selection. To address this issue we used recombination-activating gene (Rag)-deficient H-2b mice expressing a transgenic TCR restricted by I-Ed class II MHC molecules. After engraftment with Rag−/− H-2d fetal thymi, CD4+8− peripheral T cells emerged. These cells were isolated and transferred into immunodeficient hosts of H-2b or H-2d haplotype, some of the latter being common cytokine receptor γ chain deficient to exclude rejection of H-2b donor cells by host natural killer cells. Our results show that in the absence, but not in the presence, of selecting MHC molecules, peripheral mature T cells are short lived and disappear within 7 wk, indicating that continuous contact of the TCR with selecting MHC molecules is required for survival of T cells.

Download Full-text

Binding of purified, soluble major histocompatibility complex polypeptide chains onto isolated T-cell receptors. I. Reactivity against allo- and self-determinants.

Journal of Experimental Medicine ◽

10.1084/jem.150.5.1084 ◽

1979 ◽

Vol 150 (5) ◽

pp. 1084-1095 ◽

Cited By ~ 16

Author(s):

H Binz ◽

H Frischknecht ◽

C Mercolli ◽

S Dunst ◽

H Wigzell

Keyword(s):

Major Histocompatibility Complex ◽

T Cell ◽

T Cell Receptors ◽

Sodium Dodecyl ◽

Cell Receptor ◽

Third Party ◽

Major Histocompatibility ◽

Cell Receptors ◽

Histocompatibility Complex ◽

Polypeptide Chains

In this study, we tried to get information about the fine antigen-binding ability of purified, soluble, idiotype-positive T-cell receptor molecules. Lewis anti-DA T-cell receptors were purified from normal Lewis serum by the use of anti-idiotypic immunosorbent and sodium dodecyl sulfate-polyacrylamide gel, and were coupled to cyanogen bromide-activated Sepharose 4B. In parallel, Lewis anti-DA, Lewis anti-BN, and DA anti-Lewis alloantibody immunosorbents were prepared. The major Ag-B chain (44,000 daltons) and the two polypeptide chains (34,000 and 27,000 daltons) of Ia were purified from Lewis, DA, and BN lymphocytes and absorbent on the above-mentioned immunosorbents. We found that the major Ag-B chain as well as the two Ia chains were bound to the alloantibody columns if they were derived from the corresponding allogeneic strain. No retaining ability for self-major histocompatibility complex (MHC) or third-party MHC chains was noted with the alloantibody immunosorbents. When using immunosorbents made up of idiotypic T-cell receptors, only two MHC polypeptides of the relevant allo-MHC type were retained, namely, the Ag-B and the heavy Ia chains. No detectable activity was observed when testing the same column for reactivity against third-party MHC polypeptide chains. However, the Lewis anti-DA T-cell receptors could be shown to display weak, but significant, reactivity toward one Lewis MHC polypeptide chain, that is, the heavy chain of Ia type.

Download Full-text