Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B...
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Transcript of Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B...
![Page 1: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/1.jpg)
Epitopes:
Lymphocytes recog. specific sites on molecules Ag determinant/epitope
With some Ag, B cells recog 1 part; T cells another
The recognition process differs between B’s and T’s:• B cells recog soluble Ag; to highly exposed sites
• T cells recog Ag ONLY in assoc with the peptides of MHC self Ag
![Page 2: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/2.jpg)
B cell epitopes
• determined by the nature of the Fab site• epitope can be no larger than the Ag-
binding site and binding is determined by the a.a. seq in Fab
• there is complementarity btwn a.a’s of Ag and Ab– Usually hydophilic a.a’s @ surface of Ag fit
into Fab depressions
![Page 3: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/3.jpg)
Interactions of globular proteins with antibody
• Complementary binding of aa’s on AG with aa’s of Ab
• Shape of epitope of globular proteins determined by 3° structure
![Page 4: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/4.jpg)
View of interacting surfaces – contacting a.a.’s shown in red; protruding glutamines in white on Ag
Typical binding of globular proteins
![Page 5: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/5.jpg)
Binding of smaller ligands
• Smaller ligands – i.e., small oligonucleotides, peptides, and haptens can bind in smaller crevices within Fab region
In both cases, Ag-binding takes place at the V regions of the antibody
![Page 6: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/6.jpg)
Inherent features of globular proteins
• Sequential epitopes elicit Ab attachment in or out of native protein
• Nonsequential epitopes are a.a. sequences spaced apart from one another in the 1° structure BUT are brought close together by 3° folding of the protein– The antigenicity of these epitopes depend on the
conformation of the protein remaining intact
![Page 7: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/7.jpg)
Whale myoglobin Hen egg-white lysozyme
Sequential epitope Nonsequential epitope
![Page 8: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/8.jpg)
T Cell Epitopes
• T cells do not recognize native Ag∴conformational changes to proteins does not
affect their role as T cell epitope!• They only recognize Ag that has been
processed and presented with MHC molecules
• This process requires APC’s
![Page 9: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/9.jpg)
Ag’s form tri-molecular bonds with TCR and MHC
• T cell epitopes must bind with both MHC and TCR molecules
• Ag-processing is required
• Epitopes recognized are usually internal peptides of the protein
![Page 10: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/10.jpg)
B-cell epitope on HEL
Vs.
![Page 11: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/11.jpg)
Haptens
• Haptens = small, organic molecules that are antigenic, but not immunogenic
• When haptens bind to a “carrier” molecule (producing a hapten-carrier conjugate), they can become immunogenic
• Antibodies can be formed for:– Hapten epitope– Carrier epitope– Combinations of hapten and carrier
![Page 12: Epitopes: Lymphocytes recog. specific sites on molecules Ag determinant/epitope With some Ag, B cells recog 1 part; T cells another The recognition process.](https://reader034.fdocuments.in/reader034/viewer/2022051007/5a4d1afd7f8b9ab059984ec6/html5/thumbnails/12.jpg)
Experiment using BSA carrier with DNP hapten