7. Mhc Proteiny - Cas

7. Mhc Proteiny - Cas

Vclav Hoej stav molekulrn genetiky AV R MHC (HLA) GLYKOPROTEINY A JEJICH MOLEKULRN PBUZN

MHC GLYKOPROTEINY (klasick) CENTRLN MOLEKULY IMUNITY MHC gp I EXPRESE NA VECH JADERNCH BUKCH

MHC gp II EXPRESE NA APC FUNKCE VYSTAVOVAT NA POVRCHU BUKY VZORKY FRAGMENT ENDOGENNCH (MHC gp I) RESP. EXOGENNCH (MHC gp II) PROTEIN. TYTO KOMPLEXY JSOU PAK ROZEZNVNY T-LYMFOCYTY (T h, Tc)

POLYMORFISMUS: DLEIT PRO LEP OCHRANU JEDINCE I POPULACE (KOMPLIKACE TRANSPLANTACE) OBJEV: 1)OBJASNN ODHOJOVN TRANSPLANTT

(Nobelova cena 1980 - Snell, Dausset, Benacerraf) 1) FYZIOLOGICK ROLE (MHC RESTRIKCE) (Nobelova cena 1996 Doherty, Zinkernagel) LIDSK

MY MHC I HLA-A, -B, -C

MHC I H-2K, D, L **************************************************************** Ib E, F, G

Ib Qa, TL, H-2M3 CD1, MR1 CD1, MR1 ******************************************************************

HFE, FcRn, ZAG, MICA, MICB, ULBP ****************************************************************** MHC II DR, DQ, DP

(DM, DO) MHC II I-A, I-E

(DM, DO) MHCI ve krat peptidy cca 8-10 aminokyselin MHCII ve del peptidy cca 15-35 aminokyselin

ZCELA MIMODN POLYMORFISMUS MHC PROTEIN: Variabilita je v aminokyselinch ve vazebnm mst pro peptidy ! POLYMORFISMUS DLEIT PRO LEP OCHRANU JEDINCE I POPULACE

(KOMPLIKACE TRANSPLANTACE) MHC gp Motiv

HLA-11 xxAspxxxxxTyr

HLA-A2,1 xLeuxxxxxxLeu(VaI) HLA-A11

xVaIxxxxxxLys HLA-A24

xTyrxxxxxxLeu(Phe) HLA-B7 xProArgxxxxxLeu

HLA-B27 xArgxxxxxxLys(Arg)

ASOCIACE S (AUTOIMUNITNMI) CHOROBAMI Onemocnn

HLA Relativn riziko*

Ankylozujc spondyloartritida (Bechtrevova choroba) B27

87.4 Uveitida

B27 10 Goodpasteurv syndrom

DR2 15.9

Roztrouen sklerza DR2 4.8

DR3 3.7

Systmov lupus erytematodes DR3

5.8 Myasthenia gravis DR3

2.5 Pemphigus

DR4 14.4 Revmatoidn artritida

DR4 4.2

Hashimotova tyreoiditida DR5 3.2

Graves-Basedowa choroba BIOSYNTZA MHC I

BIOSYNTZA MHC II BIOSYNTZA MHC II VJIMKY ZE STANDARDNCH MECHANISM

ANTIGENN PREZENTACE Prezentace exogennch protein na MHCI (zken prezentace, crosspresentation)

Prezentace endogennch protein na MHCII (autofgie) ALOREAKTIVITA T-LYMFOCYT

VZNAM MHC I PRO FUNKCI NK-LYMFOCYT NK LYMFOCYTY

ZABJEJ BUKY S ABNORMLN NZKOU EXPRES MHC I (typick pro vtinu ndorovch bunk, kter tak unikaj ataku Tc) VE SPOLUPRCI S PROTILTKAMI ADCC

ZABJEN BUNK S DEFEKTEM MHC I HLA-E, -F, -G (MHC Ia) HLA-E (F): vazba signlnch peptid z HLA-A,B,C,G;

inhibin interakce s NK bukami HLA-G: nkolik membrnovch a sekretovanch forem, exprese na trofoblastu, interakce s inhibinmi receptory NK bunk v placent zsadn pro toleranci plodu

CD1 (MHC Ib) CD1a,b,c,e: Prezentace hydrofobnch mykobakterilnch

molekul (lipopeptidy, kys. mykolov) T lymfocytm (soust obrannch mechanism) CD1d: Prezentace (glyko)lipid specilnm T

lymfocytm (iNKT dleit regulan role) Mykobakteriln kyseliny mykolov NKTER LIGANDY CD1d

MR1 (MHC Ib) Prezentace metabolit vitaminu B (mikrobiln produkty) bukm MAIT (mucosal-associated

invariant T) MICA, MICB Vzdlenj podobnost s MHC I (nen asociace s b2m)

Indukce na stresovanch, infikovanch, ndorovch bukch ROLE MICA, MICB PI ROZEZNVN INFIKOVANCH BUNK

ROLE MIC PI ROZEZNVN STRESOVANCH A NDOROVCH BUNK FcRn Strukturn podobn MHC I, asociace s b2m

HFE Strukturn podobn MHC I, asociace s b2m Asociace s receptorem pro transferin (regulan role)

ZAG (zinc-2-glycoprotein; bez b2m) Sekretovan glykoprotein, regultor metabolismu lipid

Annual Reviews BUTYROFILIN 3A1 prezentace metabolit T-lymfocytm

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