Q28. Positive selection of T cells ensures
Positive selection of T cells primarily ensures MHC restriction by selecting only those T cells capable of recognizing self-MHC molecules.
Option Analysis
(A) MHC Restriction
Positive selection occurs in the thymus cortex where double-positive (CD4+CD8+) thymocytes interact with self-MHC molecules on thymic epithelial cells. Thymocytes whose T cell receptors (TCRs) bind weakly to self-MHC (with peptides) receive survival signals and mature, ensuring mature T cells can only recognize antigens presented by self-MHC—this defines MHC restriction. T cells failing this binding undergo apoptosis.
(B) Self Tolerance
Self-tolerance is established by negative selection, not positive selection. Negative selection in the thymic medulla deletes thymocytes with high-affinity binding to self-antigens on MHC, preventing autoimmunity. Positive selection precedes this and focuses on MHC recognition viability, not self-reactivity elimination.
(C) TCR Engagements
TCR engagement happens during positive selection as TCRs bind MHC-peptide complexes, but this is the mechanism, not the purpose. The goal is selecting functional TCRs restricted to self-MHC for peripheral antigen recognition, not mere engagement.
(D) Activation by Co-stimulatory Signal
Co-stimulatory signals (e.g., CD28-B7) are required for full peripheral T cell activation against pathogens, not thymic maturation. Positive selection relies on TCR-MHC affinity alone for survival, without co-stimulation.
Correct Answer: (A) MHC Restriction
Introduction to Positive Selection of T Cells Ensures MHC Restriction
Positive selection of T cells ensures MHC restriction, a critical thymic process shaping adaptive immunity for exams like GATE Life Sciences. This mechanism guarantees T cells recognize antigens only via self-MHC, vital for immune specificity. Mastering this distinguishes viable T cells early in development.
Thymic Development Stages
T cell maturation involves positive and negative selection in the thymus. Double-positive thymocytes first undergo positive selection in the cortex, binding self-MHC class I or II. Successful cells downregulate one co-receptor (CD4 or CD8), becoming single-positive and advancing.
Why MHC Restriction Matters
MHC restriction means T cells ignore unbound peptides, detecting only MHC-presented ones from infected cells. Positive selection enforces this by rescuing thymocytes with TCRs of moderate self-MHC affinity (avidity model). Without it, T cells couldn’t survey intracellular pathogens effectively.
| Feature | Positive Selection | Negative Selection |
|---|---|---|
| Location | Cortex | Medulla |
| Purpose | Ensures MHC restriction | Ensures self-tolerance |
| Outcome of Failure | Apoptosis | Apoptosis |
| Signal Strength | Weak/moderate affinity | High affinity |
Common Exam Misconceptions
Many confuse positive selection with self-tolerance (option B), but that’s negative selection’s role. TCR engagements (C) occur but aren’t the endpoint; co-stimulation (D) is peripheral. Focus on MHC restriction for MCQs.
