Genetic studies have identified more than 40 genes that show allelic variations associated with the development of allergic asthma and atopic dermatitis, as well as the predisposition to develop allergies to particular antigens. Among these genes are several that implicate CD4 T cell responses in the development of these allergic diseases. Name two genes (or gene clusters) associated with atopic diseases that indicate a central role for CD4 T cells in these diseases.

Question

Quizplus · Accepted Answer

One set of genes identified as associated to the development of atopic diseases encodes the TIM family (for T cell, immunoglobulin domain, and mucin domain). The genes in this set encode three T-cell-surface proteins (Tim-1, 2, and 3) and one protein expressed primarily on antigen-presenting cells (Tim-4). Mouse strains that carry different variants of the Tim genes differ both in their susceptibility to allergic inflammation of the airways and in the production of IL-4 and IL-13 by their T cells. In humans, inherited variation in the three human TIM genes has been correlated with airway hyperreactivity or hyperresponsiveness. A second type of inherited variation in IgE responses is linked to the HLA class II region (the human MHC class II region), and it affects responses to specific allergens, rather than a general susceptibility to atopy. IgE production in response to particular allergens is associated with certain HLA class II alleles, implying that particular peptide:MHC combinations might favor a strong T_H2 response; for example, IgE responses to several ragweed pollen allergens are associated with haplotypes containing the HLA class II allele DRB1 *1501. Many people are therefore generally predisposed to make T_H2 responses and are specifically predisposed to respond to some allergens more than others. A third possible answer to this question would be the Type II cytokine locus, encoding IL-4, IL-5, IL-9, IL-13, and GM-CSF. This is a less direct indicator of CD4 T cells, as other cell types are known to produce these cytokines in addition to T_H2 cells.

Genetic Studies Have Identified More Than 40 Genes That Show