Lecture 10-T cell development

Lecture 10-T cell development - Lymphocyte development is...

Info iconThis preview shows pages 1–4. Sign up to view the full content.

View Full Document Right Arrow Icon
1 Lymphocyte development is punctuated by checkpoints TCR and Ig repertoires are selected before cells go to periphery Random nature of VDJ rearrangement + allelic exclusion means lots of cells with failed or autoreactive receptors Selection needed in favor of cells with some receptor (no receptor death) Selection needed to remove many/most cells with highly self-reactive receptors Lymphocyte development is punctuated by checkpoints For T and B cells: – Strict staging of rearrangements – Strict compartmentalization – Delayed functional maturation – Survival/proliferation vs. death based on interactions with environment For T cells also: – Functional subtype specialization based on TCR recognition specificity – Choice of developmental program depends on TCR/ligand interaction T-cell developmental stage markers Normal wild-type mouse Recombination- deficient mouse (RAG1- or 2-, SCID, TCR b - d -) Total thymus Immature “DN” cells DN1 and DN2 cells with precursor activity also express c-kit T cell development is punctuated by checkpoints
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
2 T-lineage commitment Proliferation occurs in distinct, discontinuous phases TCR independent TCR dependent Development is linked with migration through distinct zones of the thymus thymus Notch/Delta signaling is crucial for early stages of T-cell development Precise control of TCR gene expression by rearrangement and TCR-quality control checkpoints Allelic exclusion prevents cells with a “good” rearrangement from “re-doing” the same gene
Background image of page 2
3 Three kinds of TCR complex used in thymic selection events e g g e zz e g g/d e zz e g d e zz TCR b pT a TCR b TCR a TCR g TCR d b -selection gd -selection positive and negative selection Stable assembly of complex allows enough low-grade signal to answer questions Does b chain exist?? How is binding to host MHC? Does gd complex exist?? b -selection: the first “audition” for membership in the mature T-cell population First stage when survival depends completely on T-cell specific genes (pre-TCR components) Cell needs to have expressed lymphocyte-specific recombinase (RAG) genes Cell is already programmed to express a universal
Background image of page 3

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 4
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 01/03/2012 for the course BI 144 taught by Professor List during the Fall '10 term at Caltech.

Page1 / 10

Lecture 10-T cell development - Lymphocyte development is...

This preview shows document pages 1 - 4. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online