Immune System Reconstitution and T Cell Specificity

This question explores how the immune system, specifically cytotoxic T lymphocytes (CD8+ T cells), develops its ability to recognize and kill infected cells. The key factors here are the origin of the T cell precursors (bone marrow) and the environment where they mature (thymus). This process determines the type of self-MHC molecules the T cells become restricted to.

Thymic Education and MHC Restriction

In this experiment, (A × B) F1 mice (H-2a/b) are reconstituted with bone marrow from (A × B) F1 mice and a thymus graft from Strain B mice (H-2b). Here's what happens:

• The bone marrow provides the hematopoietic stem cells, which give rise to T cell precursors. These precursors have the genetic information for both H-2a and H-2b MHC molecules.
• The thymus is the site of T cell maturation and education. The T cell precursors migrate into the Strain B thymus. The stromal cells within the Strain B thymus express H-2b MHC molecules.
• During development in the thymus, T cells undergo positive selection. Only T cells that can recognize self-MHC molecules expressed in the thymus with intermediate affinity are allowed to survive. In this case, the T cells will be positively selected based on their ability to interact with H-2b MHC molecules.
• Negative selection also occurs, eliminating T cells that react too strongly to self-antigens presented on self-MHC.
• As a result of this thymic education in a Strain B (H-2b) environment, the mature CD8+ T cells that leave the thymus will be primarily restricted to recognizing antigens presented on H-2b MHC molecules.

These H-2b restricted CD8+ T cells are then exposed to LCMV infection. This means they will develop specificity for LCMV peptides when presented on H-2b MHC.

CTL Lysis of Target Cells

Cytotoxic T lymphocytes (CTLs) kill target cells that present a specific antigen (in this case, LCMV peptides) on self-MHC molecules that the CTL is restricted to. Our CTLs are specific for LCMV and restricted to H-2b MHC. Let's analyze the target cells:

• A. Uninfected fibroblast cells from (A × B) F1 mouse (H-2a/b): These cells express H-2a and H-2b MHC. However, they are uninfected and do not present LCMV antigen. No lysis.
• B. Uninfected fibroblast cells from strain‐A mouse (H-2a): These cells express H-2a MHC. They do not express H-2b MHC, and they are uninfected. No lysis.
• C. Uninfected fibroblast cells from strain‐B mouse (H-2b): These cells express H-2b MHC. However, they are uninfected and do not present LCMV antigen. No lysis.
• D. LCMV infected fibroblast cells from (A × B) F1 mouse (H-2a/b): These cells express both H-2a and H-2b MHC and are infected with LCMV, so they present LCMV antigen. Since they express H-2b MHC, which the CTLs are restricted to, the CTLs can recognize the LCMV peptides presented on H-2b. Lysis occurs.
• E. LCMV infected fibroblast cells from strain‐A mouse (H-2a): These cells express H-2a MHC and present LCMV antigen. However, they do not express H-2b MHC, which the CTLs are restricted to. No lysis.
• F. LCMV infected fibroblast cells from strain‐B mouse (H-2b): These cells express H-2b MHC and are infected with LCMV, so they present LCMV antigen. Since they express H-2b MHC and present LCMV antigen, the CTLs can recognize them. Lysis occurs.

Summary of Target Cell Lysis

Based on the analysis, the CD8+ cytotoxic T lymphocytes from the reconstituted mice, being H-2b restricted, will lyse only the target cells that express H-2b MHC and are infected with LCMV, presenting the viral antigen. These are options D and F.