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Review
. 2012;32(4):349-72.
doi: 10.1615/critrevimmunol.v32.i4.50.

Cross-reactivity of T cells and its role in the immune system

Galina Petrova  1 , Andrea Ferrante, Jack Gorski
Affiliations
Review

Cross-reactivity of T cells and its role in the immune system

Galina Petrova et al. Crit Rev Immunol. 2012.

Abstract

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.

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Figures

Figure 1
Figure 1
The power law–like distribution of frequencies of overall (Total, blue circles) and cross-reactive (X-R, red squares) clonotypes in M158-66 repertoire. Logn-transformed values are fit to a linear regression line. The equation y=mx+b describes the regression line, where m is a slope and b is the intercept with the y axis. The distribution of cross-reactive clonotypes indicates self-similarity to the overall (total) repertoire.
FIGURE 2
FIGURE 2
Buffering immune responses against epitope perturbations in middle-aged individuals. Diagram of pMHC-shape–space (x–y plane) showing a mature repertoire against a particular epitope (rose). Height reflects number of T cells, and spread in the x–y plane represents cross-reactivity to adjacent (similar) pMHC-shape. A. The epitope mutates within the cross-reactive (X-R) zone. B. X-R clonotypes expand and are added. C. The epitope moves into a repertoire hole resulting from ignorance or negative selection. D. Epitope escapes detection. E. Epitope mutates into a shape in the X-R neighborhood of a different epitope (blue). F. X-R clonotypes from second repertoire expand to counteract perturbation.
See this image and copyright information in PMC

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