PCB 3233 Lecture Notes - Lecture 4: Antigen-Presenting Cell, Thymocyte, Stromal Cell

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2 Apr 2020

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T-cells originate in the bone marrow as stem cells and develop in the thymus. Migrate through the blood to the thymus. Thymus is not involved in lymphocyte recirculation. Positive: checking if tcr can recognize 1 of 12 mhc: most will die at (+) selection, occurs in the cortex. Negative: checking if tcr is autoreactive: central tolerance, occurs in the medulla. Negative selection can take place during positive selection. Everything involved with development of t-cell occurs in the cortex(outer) of the thymus except negative selection, which takes place in the medulla(inner) The medulla has bone marrow derived professional antigen presenting cells to test tcr: dendritic, b-cells, macrophages. As thymocytes mature they move from the outer region to the inner region of the thymus. Uses an autoimmune regulator (aire) for production of self-peptides in the periphery for testing on tcr: ex: insulin peptides produced by the liver can be produced. Peripheral tolerance occurs outside of the thymus.

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Question 4 (9 points):

To study T cell development, and self-restriction of T cells, you decide to perform some experiments. You obtain four mouse strains: B, B-MCC, K, and K-MCC. B strain mice express MHC molecules of the b haplotype (e.g. H-2K^b, H-2D^b, I-A^b) while K mice express MHC of the k haplotypes (e.g. H-2K^k, H-2D^k, I-A^k). The strains are otherwise genetically identical. B-MCC and K-MCC are identical to the B and K strains (respectively) excepts that contain a transgene encoding the antigen Moth Cytochrome which is not present in normal mice. MCC is produced as both a secreted and cytoplasmic protein and it is expressed by dendritic cells and thymic epithelial cells. You lethally irradiate groups of mice from all four strains and perform all possible bone marrow transfers among the mice. In other words, the BM of each strain is transplanted into mice of each strain, producing 16 different combinations of donor BM and recipient strain. You now take T cells from the lymph nodes of each of the 16 types of transplanted mice and test their ability to proliferate in response to MCC-presenting B cells that express only class II MHC molecule, I-A^k. Fill out the chart below by indicated which mice will have T cells that respond. Use (+) to indicated proliferation and NR to indicate a lack of proliferation. In addition, for the mice labelled a-e give a brief explanation for your answer. Include the mechanism of T cell selection experienced in thymus (positive selection, negative selection, or neglect) and the cells involved in selection (thymic epithelial cels, BM-derived APCs, or both).

Table (4 points, 0.25 points per box)

Recipient Strain Â®

BM Donor	B	B-MCC	K	K-MCC
B			c.
B-MCC			d.
K	a.	b.	e.
K-MCC

1 point for each explanation

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PCB 3233 Lecture Notes - Lecture 4: Antigen-Presenting Cell, Thymocyte, Stromal Cell

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