The adaptive immune system retains a cellular “memory” for antigens, enabling a stronger and more rapid response to subsequent encounters with a given pathogen. The T cell receptor (TCR) complex exists on the surface of resting T cells as monomers and oligomers of different size; antigenic stimulation leads to formation of TCR microclusters (containing about 100 TCRs) at the T cell–antigen-presenting cell (APC) interface before formation of the immune synapse (see Saito). Kumar et al. combined immunogold labeling with electron microscopy (EM) to determine the size of TCR oligomers on human peripheral blood T lymphocytes and on activated T lymphoblasts and determined that the latter had more and larger TCR oligomers than did the naïve T cells (a process that occurred over the course of several days). Consistent with these results, immunoblot analysis of membrane fractions after blue native polyacrylamide gel electrophoresis showed an increase in the ratio of TCR oligomers to monomers in the activated cells. EM analysis of mouse naïve and memory T cells revealed that resting memory T cells also had more and larger oligomeric TCR clusters than did naïve T cells. Analyses of naïve, activated, or memory ovalbumin-specific OT-1 TCR-transgenic T cells (enabling comparison of cells expressing identical TCRs) indicated that antigen sensitivity correlated with enrichment for oligomeric TCR complexes. T cell lines bearing a mutant form of the TCR subunit CD3ζ (L19A CD3ζ, in which a leucine residue postulated to be involved in oligimerization was substituted with alanine) retained the ability to form TCR complexes. However, they formed fewer and smaller oligomeric TCR complexes compared to cells with wild-type CD3ζ and showed decreased antigen sensitivity. Similarly, mouse T cells carrying the L19A CD3ζ mutation bore cell surface TCR complexes but showed reduced numbers of oligomeric complexes and decreased sensitivity to antigen, as well as an impaired memory cell response. Thus, the authors postulate that the increased presence of preexisting nanoclusters of oligomeric TCRs on memory cells enables them to mount a more vigorous response to antigen.
R. Kumar, M. Ferez, M. Swamy, I. Arechaga, M. T. Rejas, J. M. Valpuesta, W. W. A. Schamel, B. Alarcon, H. M. van Santen, Increased sensitivity of antigen-experienced T cells through the enrichment of oligomeric T cell receptor complexes. Immunity 35, 375–387 (2011). [PubMed]
T. Saito, Nanocluster formation: More with memory. Immunity 35, 318–320 (2011). [Online Journal]