Molecular mimicry and the T-cell repertoire

T cell allorecognition via molecular mimicry.

T cells often alloreact with foreign human leukocyte antigens (HLA). Here we showed the LC13 T cell receptor (TCR), selected for recognition on self-HLA-B( *)0801 bound to a viral peptide, alloreacts with B44 allotypes (HLA-B( *)4402 and HLA-B( *)4405) bound to two different allopeptides. Despite extensive polymorphism between HLA-B( *)0801, HLA-B( *)4402, and HLA-B( *)4405 and the disparate se...

Molecular Mimicry and T Cell–mediated Autoimmune Disease

B oth T cell tolerance and productive T cell responses require the interaction of the TCR with specific MHC–peptide ligands, triggering a cascade of signals that ultimately can lead to either proliferation or cell death (1– 3). These two opposing processes, which can occur during both peripheral T cell activation and/or positive/negative selection of T cells in the thymus, seem to be tuned by t...

Shaping the T cell repertoire.

Disease mimicry--a pathogenetic concept for T cell-mediated autoimmune disorders triggered by molecular mimicry?

Molecular mimicry is considered as a mechanism by which infectious pathogens may break immunological tolerance and cause autoimmune disease. It implicates that peptides shared between pathogen and host may induce cross-reactive immune reactions. According to this hypothesis, the resulting autoimmune response actually represents a secondary immune response. It is mediated by cross-reactive T cel...

The shaping of the T cell repertoire.

By combining a TCRbeta transgene with a TCRalpha minilocus comprised of a single V and two J gene segments, we engineered a mouse line exhibiting ample but focused TCR diversity, restricted to CDR3alpha. Using single-cell PCR and high-throughput sequencing, we have exploited this system to scrutinize T cell repertoire selection and evolution. Some striking observations emerged: (1) thymic selec...