Figure 2. MHC restriction and the impact of self-recognition on peripheral T cell function.

(A) Schematic of the role of self-pMHC interactions in the function of peripheral naïve CD4⁺ T cells that have been described. Clockwise from top left: T cells obtain trophic signals from interacting with self-pMHC that are required for their survival and, in lymphopenic conditions, lead to cell division; CD4⁺ T cells, but not CD8⁺ T cells, are retained in secondary lymphoid organs (SLOs) by contact with self-pMHCII-bearing dendritic cells; self-pMHC can act as co-agonists during activation with rare agonist pMHC; recognition of self-pMHC increases T cell sensitivity to foreign antigens by polarizing the TCR distribution in the cell membrane. (C) Graph depicting the direct relationship between self and foreign pMHC reactivity and the dominance of T cells with greater self-pMHC reactivity in a response to foreign antigen. Shades of blue are used to indicate surface CD5 expression levels prior to antigen recognition.