T-cell receptors recognize peptides presented by the major histocompatibility complex (MHC) on the surface of antigen-presenting cells (APC). The ability of the T-cell receptor (TCR) to recognize more than one peptide-MHC structure defines cross-reactivity. Cross-reactivity is a documented phenomenon of the immune system whose importance is still under investigation. There are a number of rational arguments for cross-reactivity. These include the discrepancy between the theoretical high number of pathogen-derived peptides and the lower diversity of the T-cell repertoire, the need for recognition of escape variants, and the intrinsic low affinity of this receptor–ligand pair. However, quantifying the phenomenon has been difficult, and its immunological importance remains unknown. In this review, we examined the cases for and against an important role for cross reactivity. We argue that it may be an essential feature of the immune system from the point of view of biological robustness.

Renal T-cell infiltration is a key component of salt-sensitive hypertension in Dahl salt-sensitive rats. Here we use an electronic servo-control technique to determine the contribution of renal perfusion pressure to T-cell infiltration in the Dahl salt-sensitive rat kidney. An aortic balloon occluder placed around the aorta between the renal arteries was used to maintain perfusion pressure to the left kidney at control levels, approximately 128 mmHg, during 7-days of salt-induced hypertension while the right kidney was exposed to increased renal perfusion pressure which averaged 157 ± 4 mmHg by high salt day-7. The number of infiltrating T-cells was compared between the two kidneys. Renal T-cell infiltration was significantly blunted in the left servo-controlled kidney compared to the right uncontrolled kidney. The number of CD3+, CD3+CD4+ and CD3+CD8+ T-cells were all significantly lower in the left servo-controlled kidney. This effect was not specific to T-cells since CD45R+ (B-cells) and CD11b/c+ (monocytes and macrophages) cell infiltrations were all exacerbated in the hypertensive kidneys. Increased renal perfusion pressure was also associated with augmented renal injury, with increased protein casts and glomerular damage in the hypertensive kidney. Levels of norepinephrine were comparable between the two kidneys, suggestive of equivalent sympathetic innervation. Renal infiltration of T-cells was not reversed by the return of renal perfusion pressure to control levels after 7-days of salt-sensitive hypertension. We conclude that increased pressure contributes to the initiation of renal T-cell infiltration during the progression of salt-sensitive hypertension in Dahl salt-sensitive rats.