You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


T cells respond to antigens in the context of major histocompatability complex (xe2x80x9cMHCxe2x80x9d) molecules. Cytotoxic T cells respond to antigens in the context of MHC class I molecules, while helper T cells respond to antigens in the context of MHC class II molecules (for review, see Davies, H., 1997, Introductory Immunobiology, Chapman and Hall, New York, pp. 177-223). Class I molecules are comprised of a heavy xcex1 chain and a xcex22-microglobulin light chain; class II molecules are heterodimers comprised of xcex1 and xcex2 chains, each having two domains and being of approximately the same length. The DNA regions containing MHC genes have been well characterized for mouse and man. The mouse MHC is referred to as the xe2x80x9cH-2 complexxe2x80x9d and the human MHC is referred to as the xe2x80x9cHLA complexxe2x80x9d (for Human Leukocyte Antigen). Class I molecules are encoded at the A, B and C loci in man and the K, D, and L loci in mouse. Class II molecules are encoded at the DP, DQ and DR regions in man and the I-A and I-E regions in mouse. At each region, a multitude of alleles has been identified.
The interaction between MHC-peptide complexes expressed on antigen presenting cells (APC) and T cell receptors (TCR) expressed on T cells leads to various T cell functions including proliferation and cytokine secretion, differentiation toward various cell subsets, anergy and apoptosis. See Davis et al. (1998) Ann. Rev. Immunol. 16:523-544. Various attempts have been made to mimic these immunomodulatory effects with soluble MHC-peptide complexes. For example, MHC molecules have been extracted from cell membranes and subjected to peptide elution followed by exchange for specific peptides in vitro. (Nag et al. (1996) Cell. Immunol. 170:25-33; Sharma et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88:11465-11469; Spack et al. (1995) J. Autoimmunity 8:787-807). Also, MHC molecules have been produced recombinantly and then loaded with peptides in vitro (Abastado et al. (1995) J. Exp. Med. 182: 439-447; Altman et al. (1996) Science 274: 94-96; Godeau et al. (1992) J. Biol. Chem. 267:24223-24229; Scheirle et al. (1992) J. Immunol. 149:1994-1999; Scott et al. (1996) J. Exp. Med. 183:2087-2095; Stem et al. (1992) Cell 68:465-477). Other attempts include the production of genetically engineered, covalently-linked peptide/MHC chimeras (International Patent Application Publication No. WO95/23814; Kozono et al. (1994) Nature 369:151-154; Mottez et al. (1995) J. Exp. Med. 181:493-502; Rhode et al. (1996) J. Immunol. 15:4885-4891; and U.S. Pat. No. 5,869,270).
A major disadvantage of monovalent MHC II-peptide ligands is that they are recognized by cognate TCRs with low avidity. The on-rates at 25xc2x0 C. vary from very slow (1,000) to moderately fast (200,000), whereas the off-rates are in a relative narrow range (0.5-0.01), or to a txc2xd of 12-30 seconds. Rates are estimated to be 2-3 times faster at physiologic temperature (Matsui et al. (1991) Science 254:1788-1791; Matsui et al. (1994) Proc. Nat. Acad. Sci. USA 91:12862-12866). In general, TCR exhibits 2 to 3-times lower binding affinity for the monovalent MHC II-peptide complex than for clonotypic antibodies to MHC-peptide complexes (Porgador et al. (1997) Immunity 6:715-726; Dadaglio et al. (1997) Immunity 6:727-738).
Recently, multivalent MHC II-peptide ligands with increased avidity for the cognate TCRs have been generated. A soluble bivalent MHC-II peptide ligand on an immunoglobulin scaffold, which binds stably and specifically to cognate TCR on T-cells, has been engineered. (Casares et al. (1997) Protein Engineering 10:1295-1301; International Patent Application Publication No. WO99/09064). Bivalent MHC II-peptide ligands engineered on an immunoglobulin scaffold exhibit approximately 20 to 25 times lower off-rates than the monovalent forms (Appel et al. (2000) J. Biol. Chem. 275:312-321). U.S. Pat. No. 6,211,342 discloses divalent MHC complexes that may be loaded with a peptide. Reich et al. expressed a BirA-dependent biotinylation site on xcex2-chain of MHC class II molecules to engineer tetravalent MHC II-peptide ligands through the streptavidin-mediated cross linking (Reich et al. (1997) Nature 387:617-620). Tetravalent MHC II/peptide ligands were successfully used to identify low-frequency antigen-specific T-cells in the peripheral blood of patients with HIV infection (Crawford et al. (1998) Immunity 8:675-682). However, the tetravalent MHC II/peptide ligands did not exceed the avidity of immunoglobulin-based, dimeric MHC II/peptide ligands, presumably because of the rigidity of biotin-streptavidin bonds that may not provide optimal accommodation of the tetramers on the TCR motifs.
Although the tetrameric MHC II-peptide molecules generated through the biotin-streptavidin bonds are valuable tools for in vitro investigation, the non-covalent nature of this bonds raises the concern of its stability in vivo. Accordingly, there is a need in the art for multimeric MHC II-peptide molecules that maintain structural integrity in vivo and exhibit immunomodulatory effects on T cells.
The present invention provides a complex comprising at least two chimeric molecules, wherein each chimeric molecule comprises an immunoglobulin constant region element having two heavy chains, wherein each heavy chain is linked to an MHC element, and wherein a peptide of interest is associated with each of the MHC elements, and wherein at least two of the chimeric molecules are covalently linked through a carbohydrate residue of the immunoglobulin constant region element by a polyalkylene glycol linker.
The present invention further provides compositions comprising the complexes.
In another embodiment, the present invention is directed to a method of making such a complex.
The present invention also provides a method of modulating T cell function comprising administering the complex of the invention, and a method of diagnosing an autoimmune disorder using the complex of the invention.