Determinants of immunodominance for CD4 T cells

Abstract

The term immunodominance was originally defined as a restricted T cell response to a short peptide sequence derived from a given protein [1]. The question of what determines immunodominance has been a longstanding battle for the past two decades. Hundreds of papers have been written on different aspects of epitope selection during antigen processing documenting the complexity of the process. Antigen processing machinery involves several accessory molecules and chaperons coevolved with proteins of Major Histocompatibility Complex (MHC) molecules that each plays its part in epitope selection. These molecules are targeted to specialized vesicular compartments that also accommodate antigen processing enzymes called cathepsins. Within the antigen processing compartments, highly regulated pH gradient and reducing conditions and enzymes necessary for denaturation of the antigens are available and function to optimize processing of antigen and selection of the fittest for transport to the cell membrane and presentation to T cells. Despite the complexity, a cell free reductionist antigen processing system was recently reported that included only few purified proteins, but was shown to process and select physiologically relevant epitopes from full length protein antigens [2]. Because of its minimalist nature the system has been quite helpful in dissecting the factors that contribute to epitope selection during antigen processing. In this review, we would summarize and highlight models that may explain how the dominant epitope may be selected for presentation to CD4+ helper T cells.

Pathogenic CD4 + T cells in patients with asthma

“…81,87,88 Such immunodominant T-cell epitopes bind to different MHCII molecules in a promiscuous fashion, which might involve multiple binding registers involving different anchor residues. A common epitope-mapping approach uses synthetic overlapping peptides spanning the entire length of the amino acid sequence of the allergen to stimulate T-cell responses in vitro .…”

Characterization of a non-classical MHC class II gene in the vulnerable Chinese egret (Egretta eulophotes)

“…In general, polymorphic class IIa molecules bind and present Electronic supplementary material The online version of this article (doi:10.1007/s00251-015-0846-1) contains supplementary material, which is available to authorized users. peptide antigens, while low-polymorphic class IIb molecules serve as chaperones and accessory proteins assisting with folding, transport, antigenic peptide loading, and editing (Hughes 1999;Alfonso and Karlsson 2000;Neefjes et al 2011;Kim and Sadegh-Nasseri 2015). The criteria routinely used to distinguish class IIb genes from class IIa genes are low polymorphism, restricted tissue distribution (e.g., tissue specificity), and/or divergent sequential structure (Klein and Figueroa 1986;Servenius et al 1987;Carrington et al 1993;Kropshofer et al 1999;Alfonso and Karlsson 2000;Glaberman et al 2008;Harstad et al 2008).…”

Broad-Based CD4+ T Cell Responses to Influenza A Virus in a Healthy Individual Who Lacks Typical Immunodominance Hierarchy

“…Multiple determinants, especially peptide generation, DM-mediated peptide exchange (editing), and responding T cell repertoire are involved in the establishment of immunodominance hierarchy (31). However, the most important determining element, often under discussed, is restricting MHC as in the syngeneic murine systems, the MHC is pre-fixed and often seeming outside the consideration.…”