Vα and Vβ Public Repertoires Are Highly Conserved in Terminal Deoxynucleotidyl Transferase-Deficient Mice

Abstract

T cell repertoires observed in response to immunodominant and subdominant peptides include private, i.e., specific for each individual, as well as public, i.e., common to all mice or humans of the same MHC haplotype, Vα-Jα and Vβ-Dβ-Jβ rearrangements. To measure the impact of N-region diversity on public repertoires, we have characterized the αβ TCRs specific for several CD4 or CD8 epitopes of wild-type mice and of mice deficient in the enzyme TdT. We find that V, (D), J usage identified in public repertoires is strikingly conserved in TdT°/° mice, even for the CDR3 loops which are shorter than those found in TdT+/+ animals. Moreover, the 10- to 20-fold decrease in αβ T cell diversity in TdT°/° mice did not prevent T cells from undergoing affinity maturation during secondary responses. A comparison of the CDR3β in published public and private repertoires indicates significantly reduced N-region diversity in public CDR3β. We interpret our findings as suggesting that public repertoires are produced more efficiently than private ones by the recombination machinery. Alternatively, selection may be biased in favor of public repertoires in the context of the interactions between TCR and MHC peptide complexes and we hypothesize that MHCα helices are involved in the selection of public repertoires.

Individual Vγ2-Jγ1.2+ T cells respond to both isopentenyl pyrophosphate and Daudi cell stimulation: generating tumor effectors with low molecular weight phosphoantigens

“…Unlike the starting αβ T cell repertoire, we found numerous examples of public Vγ2 clonotypes in the starting repertoire nearly all of which expressed the Jγ1.2 segment; selection produced an astonishingly similar repertoire among unrelated individuals. Similar to what has been observed for public αβ T cell repertoire, public Vγ2 clonotypes have minimal CDR3 diversity and are predominantly composed of germline-encoded residues [19]. Historically, the disproportionate engagement of MHC molecules with CDR1/2 of the αβ TCR was proposed to explain the phenomenon of public responses with minimal CDR3 diversity in these cells [19].…”

Convergent recombination shapes the clonotypic landscape of the naïve T-cell repertoire

“…Irrespective of the selection processes that determine the recruitment of individual pMHC epitope-specific clonotypes into the memory T-cell pool, these observations indicate that such shared, or "public," TCRs must first be present in the naïve T-cell repertoire of multiple individuals. Furthermore, it has been suggested that public TCR sequences might be generated more efficiently during the recombination process, thereby explaining differential interindividual frequencies of naïve T-cell clonotypes (5,6).…”

T Cell Repertoire Diversity Is Required for Relapses in Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis

“…Importantly, relapse in wt animals is not due to epitope spreading but to MOG-specific T lymphocytes expressing new public V␣ and V␤ rearrangements containing N additions. As reported for various ID epitopes (22,23), MOG 35-55-specific public T cell repertoires of TdT ϩ and TdT Ϫ/Ϫ littermattes are closely similar. Wt and TdT Ϫ/Ϫ mice share the public CDR3␤ sequence GETGGNYAEQ (Ref.…”

“…Shorter CDR3␤ sequences are also found in LNC and cells infiltrating the CNS of TdT Ϫ/Ϫ mice: GGTGDAEQ (two of five for LNC and two of five for CNS-infiltrating cells), GDAGDAEQ (two of five and one of five) and AGTGDAEQ (two of five and two of five). These shorter CDR3␤ sequences are characteristic of TdT Ϫ/Ϫ rearrangements as reported for naive T lymphocytes (21,30) and T cells specific for various protein epitopes (22,23,31).…”

“…The repertoire of TdT-deficient mice (TdT Ϫ/Ϫ ) is characterized by shorter CDR3s (20), and the ␣␤ TCR diversity is diminished by a factor of 10 -20 with no compensatory mechanism counterbalancing this decrease (21). Nonetheless, TdT Ϫ/Ϫ mice are not immunodeficient (22) and respond to viruses and protein Ags (22,23). Moreover, epitope immunodominance is unaltered in TdT Ϫ/Ϫ animals (22).…”