1. Marker Legend
   1. Coeliac Disease (2003). The Lancet. 362:383-91
   2. Coeliac Disease (2009). The Lancet. 373:1480-93
   3. Structural Basis for Gluten Intolerance in Celiac Sprue (2002). Science. 297:2275-2279
2. Introduction and Theoretical Framework
   1. Introduce Celiac Disease
      1. Disease Characteristics
         1. Genetically-determined Chronic inflmmatory intestinal disease
         2. Induced by environmental stimulant - gluten
         3. Involves HLA-DQ2 or HLA-DQ8 restricted T-cell immune reaction in lamina propria and immune reaction in intestinal epithelium
            1. HLA-DQ2 is expressed in more than 90% of people with coeliac disease
            2. Expression of HLA-DQ2 or HLA-DQ8 molecule is necessary but not sufficient to develop the disease
      2. Association with human population
         1. Common, worldwide prevalence is one in 266 people
      3. Signs, symptoms and consequences
         1. Increase rate of osteoporosis, infertility, autoimmune diseases, and malignant disease, especially lymphomas
         2. Gluten induces an inflammatory response, leading to the destruction of villous structure of the intestine
   2. Causation
      1. Environmental Trigger
         1. Gluten
            1. Fraction 1 - Gliadins
            2. Fraction 2 - Glutenins
            3. Composite of two proteins Gliadin and Glutenins
            4. Several epitopes are immunostimulatory, some are more active than others. An immunodominant peptide of 33 aminoacids identified from an a-gliadin fraction has functional properties attributable to many proline and glutamine residues
            5. In an experiment, gluten (a-gliadin) was digested with gastric and pancreatic enzymes and analyzed, a relatively large fragment, the 33-mer LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF was discovered. This 33-mer fragment remained intact whilst other proteolytic fragments were cleaved to smaller fragments. When reaction time with enzymes was extended, the 33-mer peptide remained intact despite prolonged exposure to preoteases.
            6. 33-mer is a very potent stimulator of three different HLA DQ2-restricted T cell clones derived from intestinal biopsies of Celiac Sprue patients stimulated with gluten. Each clone has been shown to recognize a distinct epitope found in the 33-mer.
            7. 33- mer is endowed ith exceptional toxic potency against the small intestinal mucosa
         2. 33-mer has central role in pathogenesis of celiac sprue
      2. Genetic Predispose Host
   3. Research Purpose
      1. Investigate the structure of the 33-mer
   4. Means and Methods
3. Statement of Problem
4. Purpose of the Study
5. Review of the Literature
6. Hypotheses
7. Design - Methods and Procedures
   1. Sampling
   2. Instrumentation
   3. Data collection
   4. Data Analysis
8. Limitations and Delimitations
9. Significance of the Study
   1. Research would provide insight into the mechanism of inflammatory and autoimmune responses and lead to innovations in treatment
10. References