lecture 3- T cell development

Question 1

T cell development and selection occurs in the ___

Answer 1

thymus

Question 2

what are T cells like when they leave the bone marrow?

Answer 2

very undifferentiated

Question 3

thymus becomes less functional as people ___

Answer 3

age

Question 4

before becoming T cells, as they reside in thymus and undergo selection & development, the cells are called ___- tested for their ability to ….

Answer 4

thymocytes
bind MHC and not bind to self with high affinity

Question 5

describe the transformation of cells from bone marrow to thymus and the markers they express

Answer 5

• when enter thymus, still express molecule CD34 (stem cell marker)- identifies cell as not fully developed or differentiated
• overtime, downregulate CD34 and upregulate CD2 (marker that signals commitment to T cell lineage)
• in uncommitted progenitor cell, TCR genes (antigen receptor) still in germline configuration; after committing and having CD2, begin rearrangements of alpha and beta chains- give rise to TCR
• CD4 and CD8 not expressed in either of these stages, but after pre-TCR concludes there is a functioning heavy beta chain, becomes double positive

Question 6

name the 3 broad regions of thymus structure

Answer 6

cortex & medulla
- region between them is cortico-medullary junction

Question 7

describe pos and neg selection processes in thymus structure regions

Answer 7

after productive rearrangement of alpha and beta and double positive expression of CD4 and CD8…
1- newly committed thymocytes begin their selection journey in cortex- tested for ability to bind MHC on thymic epithelial cells- perform positive selection in cortex
2- if thymocytes are successful in pos selection signal, travel down to cortico-medullary junction- site of negative selection, mediated by dendritic cell and macrophages

Question 8

location and cells involved in positive selection of T cells

Answer 8

cortex- thymic epithelial cells

Question 9

location and cells involved in negative selection of T cells

Answer 9

cortico-medullary junction- DC’s and macrophages

Question 10

what happens during positive selection of T cells?

Answer 10

T cells are seeking to interact with MHC-peptide complexes…if it does not, TCR will die (or try to rearrange alpha chains)
- during pos selection, eliminating poor binders that have weak or no binding
- moderate and strong binding lives

Question 11

what happens during neg selection of T cells?

Answer 11

critical for eliminating strong (tight) binders
- moderate-binding T cells signaled to survive

Question 12

positive and negative selection are specific for what kind of T cells?

Answer 12

alpha/beta

Question 13

what happens to gamma/delta T cells after they successfully rearrange and express a functioning receptor?

Answer 13

just exit the thymus, enter circulation and home to the gut mucosal immune system
- do not go through pos or neg selection
- no regulation of whether they bind MHC or self too tightly

Question 14

describe the process of how a T cell becomes CD4 or CD8

Answer 14

• determined at positive selection
• TCR may bind with high affinity to MHC II or MHC I – results in signals for CD4 (MHC II) or CD8 (MHC I)
• if you receive a signal to be CD8, downregulate CD4 so when you are ready to exit thymus, only express CD*
• so…upregulate the double positive for both pos and neg selection…when leave thymus and enter circulation, only have one or the other, they are self-tolerant (not self-reactive)