Updated: 5/19/2017

Structure and Function of MHC

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Introduction
  •  Major histocompatibility complexes (MHC) are cell surface expressed proteins that
    • bind to protein peptides in a surface groove
    • present bound peptides to
      • receptors on circulating T-cells
    • participate in the
      • activation of the adaptive immune response
  •  MHC are encoded by HLA genes that are localized to several different genetic regions
    • different HLA regions encode for different types of MHC
  • Allogenic MHC can be recognized by T-cells of the adaptive immune system
    • mismatch of MHC is an important cause of transplant rejection
MHC Classes 
  • There are two different classes of MHC encoded in the human genome
    • class I MHC usually presents 
      • endogenous antigens to CD8+ killer T-cells
    • class II MHC usually presents 
      • endocytosed antigens to CD4+ helper T-cells
    • antigens may be "cross-presented" by the other MHC class in some cases
  • The two MHC classes differ in several characteristics including
    • HLA loci that encodes the gene
    • sites of expression
    • protein structure
    • antigen loading site
    • antigen loading mechanism
    • binding partners
Differences Between MHC Classes
Feature MHC Class I  MHC Class II 
HLA Loci
  • HLA-A
  • HLA-B
  • HLA-C
  • One letter
  • HLA-DP
  • HLA-DQ
  • HLA-DR
  • Two letters
Site of expression
  • All nucleated cells
  • Platelets
  • Antigen presenting cells
Protein structure
  • 1 long chain
  • 1 short chain called β2 - microglobulin
  • 2 equal length chains
  • Additional invariant chain
Antigen loading site
  • Rough endoplasmic reticulum (RER)
  • Acidified endosomes
Loading mechanism
  • Endogenous proteins are degraded by the proteosome
  • Antigenic peptides are transported into the RER by the TAP transporter
  • Antigens bind to MHC molecules directly
  • Exogenous proteins are endocytosed from the cell surface
  • Antigens are produced by degradation within the endosomal compartment
  • Antigens bind to MHC molecules after release of the invariant chain
Binding Partners
  • T-cell receptor
  • CD8 co-receptor
  • T-cell receptor
  • CD4 co-receptor


 
Disease Associations
  • Each individual possesses a set of MHC class I and class II subtypes
    • these "haplotypes" define the peptides that will be recognized
  • Some haplotypes are associated with specific diseases because they may
    • preferentially bind to certain self-peptides
    • lead to a failure of immune tolerance
MHC Subtypes Associated With Diseases
Class I Haplotype Diseases Class II Haplotype Diseases
A3
  • Hemochromatosis
DQ2/DQ8
  • Celiac disease 

B8

  • Addison disease
  • Myasthenia gravis
  • Graves disease
DR2
  • Multiple sclerosis
  • Hay fever
  • Systemic lupus erythematosis
  • Goodpasture syndrome 
B27 
  • Psoriatic arthritis
  • Ankylosing spondylitis
  • Inflammatory bowel disease
  • Reactive arthritis
DR3
  • Diabetes melliutus type I
  • Systemic lupus erythematosis
  • Graves disease
  • Hashimoto thyroiditis
  • Addison disease
- - DR4
  • Rheumatoid arthritis
  • Diabetes mellitus type 1
  • Addison disease
- - DR5
  • Pernicious anemia
  • Hashimoto thyroiditis

Referenc

 

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Questions (1)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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