Annual Review of Immunology Volume 21 2003 by Annual Reviews

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Also, thymic selection and na¨ıve T cell precursor frequencies can determine immunodominance hierarchies (59). Understanding immunodominance at a mechanistic level has been a vexing problem. Some evidence suggests that antigen presentation determines immunodominance, while other studies suggest that T cell repertoire is more important. In a comprehensive study of this issue, CD8 T cell responses to five different influenza virus–derived peptides were characterized. The results were gratifying because TCR repertoire, antigen processing efficiency, and T cell competition all contribute to the T cell response hierarchy (60).

When mice naturally lacking the Dβ2-Jβ2 cluster were immunized with HSV-1, a significant reduction of the dominant gB-specific Vβ10+ T cell subset was observed (121, 122), demonstrating that germline-encoded elements and rearrangement biases have significant effects on the magnitude and makeup of T cell responses. SGM LaTeX2e(2002/01/18) Annu. Rev. Immunol. 21:29-70. org by HINARI on 09/01/07. For personal use only. CD8 T CELL RESPONSES TO PATHOGENS P1: FHD 37 Kinetic analysis of CD8 T cell priming after HSV-1 infection demonstrates the rapidity of antigen transport by professional APCs into draining lymph nodes.

This may reflect disparate epitope presentation in spleen and mediastinal lymph nodes during the course of infection (158). γ HV68 has evolved strategies to avoid CTL detection. For example, the K3 gene encodes a zinc-finger-containing protein that diminishes antigen presentation by decreasing the half-life of newly synthesized MHC class I molecules, leading to reduced surface class I expression (159). The γ HV68 M3 gene encodes a protein that binds to a wide range of chemokines (160), potentially interfering with migration of CTL and other cells to sites of infection.

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