Questions: Imagine a genetic defect where positive selection of thymocytes occurs normally, but negative selection does not occur. Which of the following is a likely detrimental result? A. Mature thymocytes will be produced that are self-reactive, recognizing self-antigen with their TCRs B. Mature thymocytes will be produced that react to foreign cells, recognizing foreign antigen with their TCRs C. Mature CD4+ thymocytes will be produced that bind to antigen presented with MHC class I. D. Mature CD8+ thymocytes will be produced that bind to antigen presented with MHC class II.

The answer is the first one (A): Mature thymocytes will be produced that are self-reactive, recognizing self-antigen with their TCRs.

Explanation for each option:

A. Mature thymocytes will be produced that are self-reactive, recognizing self-antigen with their TCRs.

• This is correct. Negative selection in the thymus is a crucial process that eliminates thymocytes that strongly recognize self-antigens. If negative selection does not occur, self-reactive thymocytes will not be eliminated, leading to the production of mature T cells that can attack the body's own tissues, potentially causing autoimmune diseases.

B. Mature thymocytes will be produced that react to foreign cells, recognizing foreign antigen with their TCRs.

• This is incorrect. Positive selection ensures that thymocytes can recognize self-MHC molecules, which is necessary for them to respond to foreign antigens presented by these MHC molecules. The absence of negative selection does not affect the ability of thymocytes to recognize foreign antigens; it affects the elimination of self-reactive thymocytes.

C. Mature CD4+ thymocytes will be produced that bind to antigen presented with MHC class I.

• This is incorrect. CD4+ T cells are selected to recognize antigens presented by MHC class II molecules. The defect in negative selection does not alter the specificity of CD4+ T cells for MHC class II.

D. Mature CD8+ thymocytes will be produced that bind to antigen presented with MHC class II.

• This is incorrect. CD8+ T cells are selected to recognize antigens presented by MHC class I molecules. The defect in negative selection does not alter the specificity of CD8+ T cells for MHC class I.

Summary: The likely detrimental result of a genetic defect where negative selection does not occur is the production of mature thymocytes that are self-reactive, recognizing self-antigen with their TCRs. This can lead to autoimmune diseases.