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Thymocytes with T cell receptors (TCR) that have high affinity for self peptides are usually negatively selected and destroyed in the thymus. T cells with TCR that recognize peptides that differ by as little as one amino acid from a self peptide, can be positively selected and migrate to the periphery. These low affinity self reactive (LASR) T cells can become autoreactive when they are activated by a peptide that exactly matches a self peptide except for this one amino acid difference (cognate peptide). LASR T cells have the highest possible affinity to self peptides that still qualifies for positive selection in the thymus.
Animal protein sequences exactly match human proteins except for occasional amino acid differences. So animal proteins are an ideal source of peptides to activate such LASR T cells described above.
Animal protein derived peptides from the vaccines are complexed with MHC on the surface of APCs and presented to LASR T cells. The combination of innate immune system costimulation by live viruses or adjuvants in vaccines and LASR T cells encountering their cognate peptides on the surface of APCs, can result in LASR T cell activation and abrogation of peripheral tolerance.
Type 1 diabetes associated autoepitopes being located at regions of near identity to animal proteins is demonstrated.
The CCR4 receptor on T cells indicates skin homing potential and the site of initial priming. Skin homing would be expected since the animal antigen containing vaccines were administered via the subcutaneous or intramuscular route. Such CD8 T cells expressing CCR4 are involved in the destruction of beta cells.